F. Rezania, L. Mohaghegh Shalmani, R. Rahimian, A. R. Dehpour, S. Ejtemaei Mehr
{"title":"Pretreatment with clonidine caused desensitization to WIN 55,212-2 in guinea pig ileum","authors":"F. Rezania, L. Mohaghegh Shalmani, R. Rahimian, A. R. Dehpour, S. Ejtemaei Mehr","doi":"10.1111/aap.12018","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>\n \n </p><ol>\n \n \n <li>Considering the existence of cross-tolerance between clonidine and morphine besides the same interaction between morphine and WIN 55,212-2 persuaded us to verify this fact between WIN 55,212-2 and clonidine in guinea pig ileum, which is a well-known model to examine the mode of action of cannabinoids and α<sub>2</sub>-adenoceptor agonists</li>\n \n \n <li>The rectangular pulses were passed to the 0.5 g stretched ileum segments that were fixed in 20-ml organ bath. PowerLab system and Graphpad Prism were applied to record twitches and analyse the data. Electrically evoked contractions were dose-dependently inhibited by WIN 55,212-2 and clonidine (p<i>D</i><sub><i>2</i></sub>= 8.56 ± 0.41 and 7.65 ± 0.15, respectively).</li>\n \n \n <li>Tolerance to this effect could be induced by 4-h incubation with WIN 55,212-2 (3 × IC<sub>50</sub>) (<i>p</i>D<sub>2</sub> = 6.36 ± 0.26, degree of tolerance: 159.32) (<i>P </i><<i> </i>0.01) but not with clonidine (2 × IC<sub>50</sub> and 4 × IC<sub>50</sub>) for different time courses. Dose–response curve for inhibitory action of WIN 55,212-2 was shifted to the right after 4-h incubation with clonidine (3 × 10<sup>−10</sup><span>m</span>) comparing to the untreated tissues (<i>p</i>D<sub>2</sub> = 5.26 ± 0.69, degree of tolerance: 2000) (<i>P </i><<i> </i>0.001). This observation provides the evidence for the cannabinoid-noradrenergic systems interaction in the enteric nervous system as a simplified representative for central nervous system.</li>\n </ol>\n \n </div>","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2014-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/aap.12018","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Autonomic and Autacoid Pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/aap.12018","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Considering the existence of cross-tolerance between clonidine and morphine besides the same interaction between morphine and WIN 55,212-2 persuaded us to verify this fact between WIN 55,212-2 and clonidine in guinea pig ileum, which is a well-known model to examine the mode of action of cannabinoids and α2-adenoceptor agonists
The rectangular pulses were passed to the 0.5 g stretched ileum segments that were fixed in 20-ml organ bath. PowerLab system and Graphpad Prism were applied to record twitches and analyse the data. Electrically evoked contractions were dose-dependently inhibited by WIN 55,212-2 and clonidine (pD2= 8.56 ± 0.41 and 7.65 ± 0.15, respectively).
Tolerance to this effect could be induced by 4-h incubation with WIN 55,212-2 (3 × IC50) (pD2 = 6.36 ± 0.26, degree of tolerance: 159.32) (P <0.01) but not with clonidine (2 × IC50 and 4 × IC50) for different time courses. Dose–response curve for inhibitory action of WIN 55,212-2 was shifted to the right after 4-h incubation with clonidine (3 × 10−10m) comparing to the untreated tissues (pD2 = 5.26 ± 0.69, degree of tolerance: 2000) (P <0.001). This observation provides the evidence for the cannabinoid-noradrenergic systems interaction in the enteric nervous system as a simplified representative for central nervous system.