General pharmacology最新文献

1. Pharmacodynamic effects of even numbered saturated fatty acids, C4-C16, were determined on isolated canine basilar and femoral arteries precontracted with PGF2 alpha. 2. The fatty acids relaxed the precontracted vessels. 3. The basilar artery was the most sensitive vessel and caprate (C10) was the most potent acid with an EC50 of 49 microM. 4. The relaxant effect was endothelium-independent. 5. Contractions elicited by norepinephrine, serotonin, and U46619 were also inhibited. 6. Caprate (C10) given intra-arterially increased femoral blood flow in a dose-dependent manner and the dose computed to increase blood flow 50% was 1.27 microM/kg.

1. Thrombin caused a tonic contractile response in rabbit aortic strips which showed tachyphylaxis. 2. Thrombin-induced contraction was partially dependent upon extracellular calcium. 3. Contractile response by lower concentrations of thrombin was suppressed by the endothelium. This endothelial effect was blocked by methylene blue, hemoglobin, bromophenacyl bromide or removal of extracellular calcium but not by indomethacin, nordihydroguaiaretic acid or nifedipine. 4. Cyclic GMP levels were not different between the thrombin-stimulated and control strips. 5. Thrombin could not stimulate prostacyclin release from the aortic strips. 6. These results suggest that thrombin possesses a contractile action in rabbit aortic smooth muscle which is attenuated by endothelium-derived relaxing factor (EDRF) spontaneously released from the endothelium during the contraction.

1. The effect of 10 day treatment with growth hormone (GH) (1 mg/kg body weight/day) and somatostatin (SRIF) (0.25 mg/kg body weight/day) subcutaneously on the activity of 5-HT1 receptors in rat hypothalamic, pituitary and cerebral cortical membrane fractions was studied using [3H]5-HT as radioligand. 2. The administration of GH and SRIF significantly decreased the 5-HT1 binding capacity and affinity in the hypothalamus. 3. In the pituitary the 5-HT1 receptor activity was also significantly decreased after both hormonal applications. 4. In the cerebral cortex the 5-HT1 receptor affinity was significantly decreased and the binding capacity was increased. 5. The results obtained indicate that GH and SRIF decrease 5-HT1 receptor activity. 5-HT1 receptors are possibly involved in the 5-HT controlled GH feedback autoregulation mediated by SRIF.

1. The effects of (+/-)- (+)- and (-)-metoprolol, (+/-)- (+)- and (-)-pindolol, (+/-)-mepindolol and (+/-)-bopindolol on the beta 1-adrenoceptor mediated responses of the rat left atria and the beta 2-adrenoceptor mediated responses of the rat portal vein to isoprenaline have been determined. 2. Racemic and (-)-metoprolol were selective beta 1-adrenoceptor antagonists. (+)-Metoprolol was devoid of beta-adrenoceptor antagonistic activity. 3. Racemic and (-)-pindolol were potent and (+)-pindolol was a modest beta-adrenoceptor antagonist. 4. (+/-)-Mepindolol and (+/-)-bopindolol were apparently competitive antagonists of the isoprenaline beta 1-adrenoceptor mediated responses of the rat left atria but non-competitive antagonists of the isoprenaline beta 2-adrenoceptor mediated responses of the rat portal vein. 5. It is suggested that (+/-)-mepindolol and (+/-)-bopindolol are slowly dissociating beta-adrenoceptor antagonists and the non-competitive antagonism can only be detected on tissues with modest receptor reserves for maximum responses to isoprenaline.

1. The effects of the calcium agonist, Bay K 8644, on the mechanical output of skeletal muscle were studied in frog semitendinosus fiber bundles and in whole sartorius muscles. 2. Low concentrations of Bay K 8644 (less than or equal to 1 microM) had no significant influence on isometric twitches. Concentrations between 5-20 microM increased peak tension by 28.6 +/- 2.9% while higher concentrations (greater than or equal to 50 microM) initially increased then depressed twitches by 70 +/- 3.5%. 3. 10 microM Bay K 8644 also increased peak tension developed during low frequency stimulation (i.e. less than or equal to 40 Hz), slightly depressed high frequency contractions (i.e. greater than or equal to 80 Hz) but did not reduce maximal tetanic tension which occurred at about 60 Hz. 4. Potentiation of twitches and low frequency tetani and depression of high frequency tetani by Bay K 8644 were partially antagonized by nifedipine (10 microM), low extracellular calcium and D-600 (5 microM). These conditions did not, however, block the depressant actions of greater than or equal to 50 microM Bay K 8644. 5. In skinned fibers, 10 microM Bay K 8644 had no effect on resting or maximal Ca2+ activated tension. Also, 10 microM Bay K 8644 had no effect on caffeine contractures when added to the previous Ca2+ loading solution. 6. These results suggest that Bay K 8644 has both positive and negative inotropic actions on isolated skeletal muscle, which are dependent on drug concentration and muscle activation pattern.

1. Smooth muscle from six sites in the cat gastrointestinal tract was evaluated with respect to its ability to generate contractions in calcium-free solutions. 2. Membrane depolarization and carbachol, but not cholecystokinin or neurotensin, increased tension in smooth muscle segments of esophagus, corpus, duodenum, ileum, proximal colon and distal colon in calcium-free solution. 3. Substance-P produced a contractile response in the absence of calcium but only in the corpus and distal colon. 4. These findings indicate that peptide mediated release of intracellular calcium plays a minimal role in activation of cat gastrointestinal smooth muscle.

1. Thermal responses to prazosin (PRA) and dihydrobenzperidol (DHBP) (0.75 mg/kg) or nifedipin (ADA: 0.05 mg/kg) administered intravenously were investigated in hyperthermic rabbits. 2. Hyperthermia produced by dinitrophenol (DNP; 20 mg/kg; i.v.), resulted from stimulation of the metabolic rate. 3. All the investigated drugs; i.e. PRA, DHBP, ADA reduced the hyperthermic activity of DNP. Contrary to DHBP and ADA, PRA did not change DNP--stimulated metabolism. 4. Possible mechanisms responsible for prazosin antihyperthermizing action are discussed.

1. The possible antinociceptive action of GABA A receptor agonist homotaurine, has been studied through a battery of chemical (acetic acid) and thermal (hot plate, tail flick and tail immersion) tests in rats and mice. 2. The aminoacid was used at the following doses 22.25; 55.62 and 111.24 mg/kg i.p. and 50-100 micrograms i.c.v.; and measurements were made at the time of and at 5, 15 and 30 min after drug administration. 3. Homotaurine exhibited a significantly antinociceptive effect in all the above mentioned test except hot plate and when administered i.c.v. in the tail flick test. 4. The antinociceptive effect in the chemical test was dose and time dependent. 5. In the tail immersion test, latency time for withdrawal of the tail was significantly increased with the dose of 55.62 mg/kg at 15 min and 111.24 mg/kg at 30 min. 6. In the tail flick test the antinociceptive effect was dose dependent at 15 and 30 min. 7. From the above results the implication of peripheral and spinal mechanisms in the antinociceptive effect of homotaurine may be concluded.

1. The release of SPLI evoked by high levels of K+ (50 mM) from the spinal cord of diabetic rats was greater than in the case of spinal cord from control rats. 2. Morphine (10(-5) M) significantly inhibited the K(+)-evoked release of SPLI release in both the groups. However, in spinal cord from diabetic rats, morphine reduced the K(+)-evoked release of SPLI only to the levels that were observed in material from control rats prior to treatment with morphine. 3. Glucose (20 mM) and dibutyryl cyclic-AMP (10(-4) M) significantly potentiated the K(+)-evoked release of SPLI in spinal cord from control rats. 4. These findings suggest that excessive release of SPLI from the spinal cord may be associated with the reported abnormalities in nociceptive transmission in diabetic rats, and that excessive release of SPLI may be modulated by levels of glucose and/or cyclic-AMP in the spinal cord.

1. The effect of aminophylline and terbutaline sulfate, separately and in combination, on the contractility of the feline diaphragm was investigated. 2. Diaphragmatic contractility increased significantly (P less than 0.05) to 28.3% above control level as long as theophylline plasma levels were maintained between 10-20 mg/l (mean 13.9 +/- 0.8 mg/l). 3. Diaphragmatic contractility showed a significant (P less than 0.05) 41.5% increase after i.v. administration of terbutaline sulfate as a maintenance dose of 1.4 micrograms/kg-hr, and the increase leveled off after 180 min. 4. Administering the two drugs in combination showed a significant (P less than 0.05) 27.3% increase which suggests a non-synergistic effect of aminophylline and terbutaline sulfate on diaphragmatic contractility. 5. By enhancing the contractility of the diaphragm, aminophylline and terbutaline sulfate may improve the clinical status of patients with airway obstructive diseases and help in preventing respiratory muscle fatigue.