Pub Date : 2000-07-01DOI: 10.1211/146080800128736097
S. Sridevi, P. Diwan
A HPLC method has been developed for determination of gliquidone in rat plasma. The assay involves combined extraction and precipitation with 1:1 methanol-acetonitrile, and separation of the analyte on a Shimpack ODS (C18) column with 75:25 (v/v) acetonitrile-0.1 M acetic acid as mobile phase. Detection at 229 nm was by photodiode-array detection. The assay was validated in accordance with international requirements and found to be specific, accurate and precise with a linearity range from 50 ng mL−1 to 10μg mL−1. The method was suitable for conducting pharmacokinetic studies in rats.
{"title":"Validated HPLC Method for the Determination of Gliquidone in Rat Plasma","authors":"S. Sridevi, P. Diwan","doi":"10.1211/146080800128736097","DOIUrl":"https://doi.org/10.1211/146080800128736097","url":null,"abstract":"A HPLC method has been developed for determination of gliquidone in rat plasma. The assay involves combined extraction and precipitation with 1:1 methanol-acetonitrile, and separation of the analyte on a Shimpack ODS (C18) column with 75:25 (v/v) acetonitrile-0.1 M acetic acid as mobile phase. Detection at 229 nm was by photodiode-array detection. The assay was validated in accordance with international requirements and found to be specific, accurate and precise with a linearity range from 50 ng mL−1 to 10μg mL−1. The method was suitable for conducting pharmacokinetic studies in rats.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77063208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-07-01DOI: 10.1211/146080800128736123
S. Ahlénius, K. Larsson
It has previously been shown that blocking 5-HT1A receptors unmasks an inhibitory action of the selective 5-hydroxytryptamine (5-HT) re-uptake inhibitor citalopram on male rat ejaculatory behaviour. This paper reports that subcutaneous (s.c.) administration of the selective 5-HT re-uptake inhibitor citalopram (10 mgkg−1) facilitated ejaculatory behaviour in male Wistar rats treated with the 5-HT1B receptor antagonist isamoltane (4 mgkg−1, s.c.), whereas neither citalopram nor isamoltane alone had any effect. It is concluded that citalopram possesses an inhibitory action on male rat ejaculatory behaviour, and that this inhibition normally is balanced by a facilitatory action mediated via 5-HT1A receptors.
{"title":"Stimulation of Ejaculatory Behaviour by the 5‐HT1B Receptor Antagonist Isamoltane in Citalopram‐pretreated Male Rats","authors":"S. Ahlénius, K. Larsson","doi":"10.1211/146080800128736123","DOIUrl":"https://doi.org/10.1211/146080800128736123","url":null,"abstract":"It has previously been shown that blocking 5-HT1A receptors unmasks an inhibitory action of the selective 5-hydroxytryptamine (5-HT) re-uptake inhibitor citalopram on male rat ejaculatory behaviour. This paper reports that subcutaneous (s.c.) administration of the selective 5-HT re-uptake inhibitor citalopram (10 mgkg−1) facilitated ejaculatory behaviour in male Wistar rats treated with the 5-HT1B receptor antagonist isamoltane (4 mgkg−1, s.c.), whereas neither citalopram nor isamoltane alone had any effect. It is concluded that citalopram possesses an inhibitory action on male rat ejaculatory behaviour, and that this inhibition normally is balanced by a facilitatory action mediated via 5-HT1A receptors.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81742134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-07-01DOI: 10.1211/146080800128736088
Xiaoxin Zhou, S. Phadtare, K. Agrawal, V. Kishore
Complexes of Zn(II) with radioprotective thiol ligands such as cysteamine, L-cysteine and N-(2-mercaptopropionyl)glycine have been synthesized, characterized, and evaluated for cytotoxicity and radioprotective effect. Zn2(N-(2-mercaptopropionyl)glycine)2 when given intraperitoneally at a dose of 14.1 mgkg−1, 30 min before whole-body γ-irradiation (9.0 Gy, 1 Gy min−1), resulted in 68% 30-day survival of CD2F1 mice. This radioprotection was significantly better than that afforded by equimolar doses of ZnCl2 (7%), by N-(2-mercaptopropionyl)glycine (0%), or by a mixture of ZnCl2 and N-(2-mercaptopropionyl)-glycine (0%). Zn(cysteamine)2 and Zn(L-cysteine)2 afforded 14% and 7% survival of CD2F1 mice. These data show that the radioprotective effect of thiols such as N-(2-mercaptopropionyl)glycine can be enhanced by complexation with Zn(II).
{"title":"Synthesis and Radioprotective Effect of Zinc(II) Complexes with Cysteamine, Cysteine and Mercaptopropionylglycine","authors":"Xiaoxin Zhou, S. Phadtare, K. Agrawal, V. Kishore","doi":"10.1211/146080800128736088","DOIUrl":"https://doi.org/10.1211/146080800128736088","url":null,"abstract":"Complexes of Zn(II) with radioprotective thiol ligands such as cysteamine, L-cysteine and N-(2-mercaptopropionyl)glycine have been synthesized, characterized, and evaluated for cytotoxicity and radioprotective effect. Zn2(N-(2-mercaptopropionyl)glycine)2 when given intraperitoneally at a dose of 14.1 mgkg−1, 30 min before whole-body γ-irradiation (9.0 Gy, 1 Gy min−1), resulted in 68% 30-day survival of CD2F1 mice. This radioprotection was significantly better than that afforded by equimolar doses of ZnCl2 (7%), by N-(2-mercaptopropionyl)glycine (0%), or by a mixture of ZnCl2 and N-(2-mercaptopropionyl)-glycine (0%). Zn(cysteamine)2 and Zn(L-cysteine)2 afforded 14% and 7% survival of CD2F1 mice. These data show that the radioprotective effect of thiols such as N-(2-mercaptopropionyl)glycine can be enhanced by complexation with Zn(II).","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85717402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-06-01DOI: 10.1211/146080800128735971
L. Fattore, G. Cossu, M. Mascia, M. Obinu, C. Ledent, M. Parmentier, A. Imperato, G. Böhme, W. Fratta
It has been reported that, as well as morphine, the cannabinoid CB1 receptor agonist WIN 55,212-2 failed to induce intravenous self- administration in mutant CB1 receptor knockout (CB1(-/-)) mice but not in the corresponding wild type (CB1(+/+)) mice. To verify whether this functional interaction responsible for opioid rewarding effects was specific or could also be extended to other drugs of abuse, we have evaluated the ability of cocaine, amphetamine and nicotine to induce intravenous self- administration in both CB1(-/-) and CB1(+/+) mice. The results showed that, contrary to morphine, the other drugs of abuse were intravenously self- administered to the same extent by both wild type and CB1(-/-) mice. This points to a specific role of the CB1 receptor in the opioid motivational and rewarding properties. In addition, since mesolimbic dopamine transmission is known to have a pivotal role in reward mediation, the effect of morphine on limbic dopamine release in CB1(-/-) and CB1(+/+) mice has been investigated and compared with the effect of cocaine. Morphine did not modify dopamine release in the nucleus accumbens of CB1(-/-) mice whereas it dose- dependently stimulated dopamine release in the corresponding CB1(+/+) mice. In contrast, cocaine increased dopamine release in both strains of mice, showing that its effect on dopamine transmission was not linked to the cannabinoid system. Taken together, our results clearly show that the CB1 receptor is essential for the expression of the behavioural and biochemical effects of morphine. This extends previous observations on a functional specific interaction between endogenous cannabinoid and opiate systems in the central mechanisms of reward.
{"title":"Role of Cannabinoid CB1 Receptor in Morphine Rewarding Effects in Mice","authors":"L. Fattore, G. Cossu, M. Mascia, M. Obinu, C. Ledent, M. Parmentier, A. Imperato, G. Böhme, W. Fratta","doi":"10.1211/146080800128735971","DOIUrl":"https://doi.org/10.1211/146080800128735971","url":null,"abstract":"It has been reported that, as well as morphine, the cannabinoid CB1 receptor agonist WIN 55,212-2 failed to induce intravenous self- administration in mutant CB1 receptor knockout (CB1(-/-)) mice but not in the corresponding wild type (CB1(+/+)) mice. To verify whether this functional interaction responsible for opioid rewarding effects was specific or could also be extended to other drugs of abuse, we have evaluated the ability of cocaine, amphetamine and nicotine to induce intravenous self- administration in both CB1(-/-) and CB1(+/+) mice. The results showed that, contrary to morphine, the other drugs of abuse were intravenously self- administered to the same extent by both wild type and CB1(-/-) mice. This points to a specific role of the CB1 receptor in the opioid motivational and rewarding properties. In addition, since mesolimbic dopamine transmission is known to have a pivotal role in reward mediation, the effect of morphine on limbic dopamine release in CB1(-/-) and CB1(+/+) mice has been investigated and compared with the effect of cocaine. Morphine did not modify dopamine release in the nucleus accumbens of CB1(-/-) mice whereas it dose- dependently stimulated dopamine release in the corresponding CB1(+/+) mice. In contrast, cocaine increased dopamine release in both strains of mice, showing that its effect on dopamine transmission was not linked to the cannabinoid system. Taken together, our results clearly show that the CB1 receptor is essential for the expression of the behavioural and biochemical effects of morphine. This extends previous observations on a functional specific interaction between endogenous cannabinoid and opiate systems in the central mechanisms of reward.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89962274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-06-01DOI: 10.1211/146080800128735980
M. Carai, R. Agabio, C. Lobina, M. Pani, R. Reali, G. Vacca, G. Colombo, G. Gessa
The possible presence of a functional interaction in the constipating effect of opioids and cannabinoids has been assessed. We have measured the ability of the opioid receptor antagonist, naloxone, to antagonize the inhibitory effect of the cannabinoid receptor agonist, WIN 55,212-2, and also, the ability of the cannabinoid CB1-receptor antagonist, SR 141716A, to antagonize the inhibitory effect of morphine, on transit of an orally administered, non-absorbable marker (carmine) in the mouse small intestine. Naloxone failed to alter the reducing effect of WIN 55,212-2 on the propulsive activity; conversely, pretreatment with SR 141716A did not prevent morphine-induced inhibition of marker transit. These results suggest that the constipating effect of opioids and cannabinoids occur through independent and unrelated mechanisms. We assessed also the possible existence of an interaction between CB1 and dopamine D2 receptor systems. The effect of the D2-receptor antagonist, S(-)-sulpiride, on the inhibiting effect of WIN 55,212-2 and of SR 141716A on the inhibiting effect of the D2 agonist, bromocriptine, on intestinal propulsion were assessed. Combination of 50 mg kg−1S(-)-sulpiride and 0.5 mg kg−1 WIN 55,212-2, but not higher doses, resulted in the blockade of WIN 55,212-2 effect; similarly, combination of 0.1 mg kg−1 SR 141716A abolished bromocriptine-induced decrease in intestinal motility. These results suggest the existence of a functional interaction between the CB1 and D2 receptors in mouse intestinal motility.
阿片类药物和大麻素在便秘作用中可能存在的功能相互作用已被评估。我们测量了阿片受体拮抗剂纳洛酮对抗大麻素受体激动剂WIN 55,212-2的抑制作用的能力，以及大麻素cb1受体拮抗剂SR 141716A对抗吗啡在小鼠小肠中口服的不可吸收标记物(carmine)转运的抑制作用的能力。纳洛酮未能改变WIN 55212 -2对推进活性的降低作用;相反，SR 141716A预处理并不能阻止吗啡诱导的标记物转运抑制。这些结果表明，阿片类药物和大麻素的便秘作用是通过独立和不相关的机制发生的。我们还评估了CB1和多巴胺D2受体系统之间可能存在的相互作用。研究D2受体拮抗剂S(-)-舒必利对WIN 55,212-2的抑制作用和SR 141716A对D2受体激动剂溴隐亭肠推进的抑制作用的影响。50 mg kg - 1S(-)-磺必利与0.5 mg kg - 1 WIN 55,212-2联合使用，但剂量不高，可阻断WIN 55,212-2的作用;同样，0.1 mg kg−1 SR 141716A联合用药可消除溴隐亭引起的肠蠕动减弱。这些结果表明，在小鼠肠道运动中存在CB1和D2受体之间的功能相互作用。
{"title":"Relationship between Cannabinoid CB1 and Dopamine D2 Receptors in Intestinal Motility in Mice","authors":"M. Carai, R. Agabio, C. Lobina, M. Pani, R. Reali, G. Vacca, G. Colombo, G. Gessa","doi":"10.1211/146080800128735980","DOIUrl":"https://doi.org/10.1211/146080800128735980","url":null,"abstract":"The possible presence of a functional interaction in the constipating effect of opioids and cannabinoids has been assessed. \u0000 \u0000 \u0000 \u0000We have measured the ability of the opioid receptor antagonist, naloxone, to antagonize the inhibitory effect of the cannabinoid receptor agonist, WIN 55,212-2, and also, the ability of the cannabinoid CB1-receptor antagonist, SR 141716A, to antagonize the inhibitory effect of morphine, on transit of an orally administered, non-absorbable marker (carmine) in the mouse small intestine. \u0000 \u0000 \u0000 \u0000Naloxone failed to alter the reducing effect of WIN 55,212-2 on the propulsive activity; conversely, pretreatment with SR 141716A did not prevent morphine-induced inhibition of marker transit. \u0000 \u0000 \u0000 \u0000These results suggest that the constipating effect of opioids and cannabinoids occur through independent and unrelated mechanisms. \u0000 \u0000 \u0000 \u0000We assessed also the possible existence of an interaction between CB1 and dopamine D2 receptor systems. The effect of the D2-receptor antagonist, S(-)-sulpiride, on the inhibiting effect of WIN 55,212-2 and of SR 141716A on the inhibiting effect of the D2 agonist, bromocriptine, on intestinal propulsion were assessed. Combination of 50 mg kg−1S(-)-sulpiride and 0.5 mg kg−1 WIN 55,212-2, but not higher doses, resulted in the blockade of WIN 55,212-2 effect; similarly, combination of 0.1 mg kg−1 SR 141716A abolished bromocriptine-induced decrease in intestinal motility. \u0000 \u0000 \u0000 \u0000These results suggest the existence of a functional interaction between the CB1 and D2 receptors in mouse intestinal motility.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83737886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-06-01DOI: 10.1211/146080800128736006
V. Marzo
After the discovery of the endogenous ligands of cannabinoid receptors, the “endocannabinoids” anandamide (N-arachidonoyl-ethanolamine) and 2-arachidonoylglycerol, several studies have been carried out to clarify the molecular mechanisms underlying the regulation of the levels of these compounds in animal tissues. More than one biosynthetic pathway has been proposed for anandamide and 2-arachidonoylglycerol, and several routes for the inactivation of these substances have been identified also. Specific inhibitors of anandamide inactivation have been designed. More recently, the levels of these compounds have been correlated to the occurrence of some physiological and pathological situations, such as cell damage, shock, neurological disorders, pain and inflammation, brain development, and drug tolerance. Some of these studies are reviewed briefly here and have led to the proposal of the use of endocannabinoid-derived substances as analgesic and neuroprotective drugs, and to suggest a role for anandamide and 2-arachidonoylglycerol in motor disorders.
{"title":"Regulation of Endocannabinoid Levels under Physiological and Pathological Conditions. A Mini‐review","authors":"V. Marzo","doi":"10.1211/146080800128736006","DOIUrl":"https://doi.org/10.1211/146080800128736006","url":null,"abstract":"After the discovery of the endogenous ligands of cannabinoid receptors, the “endocannabinoids” anandamide (N-arachidonoyl-ethanolamine) and 2-arachidonoylglycerol, several studies have been carried out to clarify the molecular mechanisms underlying the regulation of the levels of these compounds in animal tissues. More than one biosynthetic pathway has been proposed for anandamide and 2-arachidonoylglycerol, and several routes for the inactivation of these substances have been identified also. Specific inhibitors of anandamide inactivation have been designed. More recently, the levels of these compounds have been correlated to the occurrence of some physiological and pathological situations, such as cell damage, shock, neurological disorders, pain and inflammation, brain development, and drug tolerance. Some of these studies are reviewed briefly here and have led to the proposal of the use of endocannabinoid-derived substances as analgesic and neuroprotective drugs, and to suggest a role for anandamide and 2-arachidonoylglycerol in motor disorders.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83669520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-06-01DOI: 10.1211/146080800128736060
P. Massi, A. Vaccani, D. Parolaro
Cannabinoids and opioids share several pharmacological properties, including antinociception, hypothermia, sedation, hypotension and inhibition of immune function. It has been demonstrated that chronic morphine treatment in rats produced hypersensitivity to Δ9-tetrahydrocannabinol analgesia. As a consequence of those results and the fact that drug abusers often use marijuana and morphine concurrently, we have investigated the possibility of functional interaction between opioid and cannabinoid systems at immune level in the rat. We have evaluated splenocyte proliferative response to a mitogen and natural killer cytolytic activity following chronic administration of the synthetic cannabinoid compound CP-55,940, and morphine. A psychotropic dose of CP-55,940 (0.2 mg kg−1, i.p.) significantly inhibited the splenocyte proliferative response to Concanavalin A and natural killer activity. Similar to the effects of CP-55,940, morphine (5 mg kg−1, s.c.) administration was also accompanied by a significant suppression of both parameters. Animals that received daily injection of either CP-55,940 or morphine developed tolerance to their acute immunosuppressive effects. Once tolerance to the suppressive effects of either cannabinoid or morphine was achieved, animals became cross-resistant to the suppressive effect of either drug. These data suggest the possibility that morphine and CP-55,940 have a common underlying mechanism for the suppression of splenocyte proliferation and natural killer activity.
大麻素和阿片类药物具有一些共同的药理特性，包括抗痛觉、降低体温、镇静、低血压和抑制免疫功能。已经证明，慢性吗啡治疗大鼠对Δ9-tetrahydrocannabinol镇痛产生超敏反应。由于这些结果以及药物滥用者经常同时使用大麻和吗啡的事实，我们研究了大鼠免疫水平上阿片类药物和大麻素系统之间功能相互作用的可能性。我们评估了慢性给药合成大麻素化合物CP-55,940和吗啡后，脾细胞对有丝分裂原的增殖反应和自然杀伤细胞溶解活性。精神药物剂量CP-55,940 (0.2 mg kg - 1, i.p.)显著抑制脾细胞对刀豆蛋白A的增殖反应和自然杀伤活性。与CP-55,940的作用类似，吗啡(5mg kg - 1, s.c)的施用也伴随着这两个参数的显著抑制。每天注射CP-55,940或吗啡的动物对其急性免疫抑制作用产生了耐受性。一旦对大麻素或吗啡的抑制作用产生耐受性，动物就会对这两种药物的抑制作用产生交叉抗性。这些数据表明吗啡和CP-55,940可能具有抑制脾细胞增殖和自然杀伤活性的共同潜在机制。
{"title":"Interaction between Opioids and Cannabinoids in the Immune System: Functional Evidence in the Rat","authors":"P. Massi, A. Vaccani, D. Parolaro","doi":"10.1211/146080800128736060","DOIUrl":"https://doi.org/10.1211/146080800128736060","url":null,"abstract":"Cannabinoids and opioids share several pharmacological properties, including antinociception, hypothermia, sedation, hypotension and inhibition of immune function. It has been demonstrated that chronic morphine treatment in rats produced hypersensitivity to Δ9-tetrahydrocannabinol analgesia. As a consequence of those results and the fact that drug abusers often use marijuana and morphine concurrently, we have investigated the possibility of functional interaction between opioid and cannabinoid systems at immune level in the rat. We have evaluated splenocyte proliferative response to a mitogen and natural killer cytolytic activity following chronic administration of the synthetic cannabinoid compound CP-55,940, and morphine. \u0000 \u0000A psychotropic dose of CP-55,940 (0.2 mg kg−1, i.p.) significantly inhibited the splenocyte proliferative response to Concanavalin A and natural killer activity. Similar to the effects of CP-55,940, morphine (5 mg kg−1, s.c.) administration was also accompanied by a significant suppression of both parameters. Animals that received daily injection of either CP-55,940 or morphine developed tolerance to their acute immunosuppressive effects. Once tolerance to the suppressive effects of either cannabinoid or morphine was achieved, animals became cross-resistant to the suppressive effect of either drug. \u0000 \u0000These data suggest the possibility that morphine and CP-55,940 have a common underlying mechanism for the suppression of splenocyte proliferation and natural killer activity.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90585231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-06-01DOI: 10.1211/146080800128735962
R. Toro, S. Spampinato
We have studied the effects of long-term activation of cannabinoid receptors on opioid receptor desensitization and down-regulation. The mouse neuroblastomaxrat glioma hybridoma NG 108-15 cell line was used as it represents a suitable model expressing both cannabinoid CB1 and δ-opioid receptors linked to Gi proteins. Twenty-four-hour exposure of NG 108-15 cells to the cannabinoid agonist WIN 55, 212-2 mesylate (200 nM) reduced opioid receptor binding, evaluated in intact cells, by approximately 50%. Down-regulation of δ-opioid receptors was not observed in cells exposed to pertussis toxin for 24 h. In cells that were exposed to the cannabinoid for 24 h, the ability of the δ-opioid receptor agonist [D-Ser2, Leu5, Thr6]enkephalin to inhibit forskolin-stimulated cAMP accumulation was significantly attenuated. The selective cannabinoid receptor antagonist SR 141716A blocked the effects elicited by WIN 55,212-2 on δ-opioid receptor desensitization and down-regulation. These data demonstrate the existence, in NG 108-15 cells, of a complex cross-talk between the cannabinoid and opioid receptors.
{"title":"Cannabinoids Regulate δ-Opioid Receptors in NG108-15 Hybrid Cells","authors":"R. Toro, S. Spampinato","doi":"10.1211/146080800128735962","DOIUrl":"https://doi.org/10.1211/146080800128735962","url":null,"abstract":"We have studied the effects of long-term activation of cannabinoid receptors on opioid receptor desensitization and down-regulation. The mouse neuroblastomaxrat glioma hybridoma NG 108-15 cell line was used as it represents a suitable model expressing both cannabinoid CB1 and δ-opioid receptors linked to Gi proteins. \u0000 \u0000 \u0000 \u0000Twenty-four-hour exposure of NG 108-15 cells to the cannabinoid agonist WIN 55, 212-2 mesylate (200 nM) reduced opioid receptor binding, evaluated in intact cells, by approximately 50%. Down-regulation of δ-opioid receptors was not observed in cells exposed to pertussis toxin for 24 h. In cells that were exposed to the cannabinoid for 24 h, the ability of the δ-opioid receptor agonist [D-Ser2, Leu5, Thr6]enkephalin to inhibit forskolin-stimulated cAMP accumulation was significantly attenuated. The selective cannabinoid receptor antagonist SR 141716A blocked the effects elicited by WIN 55,212-2 on δ-opioid receptor desensitization and down-regulation. \u0000 \u0000 \u0000 \u0000These data demonstrate the existence, in NG 108-15 cells, of a complex cross-talk between the cannabinoid and opioid receptors.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80681236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-06-01DOI: 10.1211/146080800128736051
D. Giuliani, A. Ottani, F. Ferrari
We have examined the effect of HU 210, a synthetic cannabinoid receptor agonist, on rat body weight and eating behaviour. HU 210 (25, 50 or 100μ kg−1) sub-chronically administered for four days, produced a dose- and time-dependent loss of body weight. At the highest dose the body weight was not regained by the seventh day after the drug was stopped, remaining markedly below that of vehicle-treated animals. Atchuand sub-chronic treatment of fasted rats with HU 210 (50 and 100μ kg−1) significantly inhibited standard food intake; this anorexic effect was still present seven days after the last injection of 100μ kg−1 HU 210. Fasted rats, familiarized with chocolate and acutely treated with HU 210 at 50 or 100μ kg−1 reduced their standard food but not chocolate consumption in a two-choice condition. The results showed that HU 210 exerted a potent and long-lasting reduction of body weight, and that it produced a disrupting effect on the consumption of standard food, but not of chocolate.
我们研究了HU 210，一种合成大麻素受体激动剂，对大鼠体重和饮食行为的影响。HU 210(25、50或100μ kg−1)亚慢性给药4天，产生剂量和时间依赖性的体重损失。在最高剂量下，停药后第7天体重没有恢复，明显低于给药动物的体重。HU 210(50和100μ kg−1)对禁食大鼠的急性和亚慢性处理显著抑制标准食物摄取量;最后一次注射100μ kg−1 HU 210后7 d仍有厌食作用。在两种选择条件下，熟悉巧克力的禁食大鼠和急性用50或100μ kg - 1的HU 210治疗的大鼠减少了它们的标准食物，但没有减少巧克力的摄入量。结果表明，HU 210对体重的降低具有有效和持久的作用，它对标准食品的消费产生了干扰作用，但对巧克力没有影响。
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Pub Date : 2000-06-01DOI: 10.1211/146080800128735953
M. Adami, S. Bertini, P. Frati, G. Soldani, G. Coruzzi
The effects of cannabinoid CB1 receptor activation (HU-210) and blockade (SR141716A) on gastric acid secretion were determined in anaesthetized rats with lumen perfused stomach. The selective CB1-receptor agonist HU-210 (0.01-0-1 mg kg−1, i.v.) did not affect basal acid secretion while causing inhibition (maximum reduction 74%) of the gastric acid secretion stimulated by pentagastrin (10μ kg−1, i.v.). The inhibitory effect of HU-210 was reversed by the selective cannabinoid CB1-receptor antagonist SR141716A (1 mg kg−1, i.v.), but not by the selective CB2-receptor antagonist SR144528 (1 mg kg−1, i.v.). These results suggest that cannabinoid CB1 receptors may mediate inhibitory effects on gastric acid secretion in the rat.
研究了大麻素CB1受体激活(HU-210)和阻断(SR141716A)对麻醉胃腔灌注大鼠胃酸分泌的影响。选择性cb1受体激动剂HU-210 (0.01-0-1 mg kg -1，静脉注射)不影响基底酸分泌，但对戊胃泌素(10μ kg -1，静脉注射)刺激的胃酸分泌有抑制作用(最大减少74%)。HU-210的抑制作用被选择性大麻素cb1受体拮抗剂SR141716A (1 mg kg - 1，静脉注射)逆转，但不被选择性cb2受体拮抗剂SR144528 (1 mg kg - 1，静脉注射)逆转。提示大麻素CB1受体可能介导大鼠胃酸分泌的抑制作用。
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