Rapid desensitization of central beta-adrenoceptors in rat after subacute treatment with imipramine and calcium entry blockers.
The subcutaneous (s.c.) administration of isoprenaline to rats produced a dose-dependent increase in water drinking which was effectively antagonized by propranolol. This dipsogenic response was significantly inhibited after the intraperitoneal (i.p.) administration of imipramine (15 mg/kg/day), together with either of the following calcium entry blockers, for four days: diltiazem (15 mg/kg/day), verapamil (10 mg/kg/day), nifedipine (10 mg/kg/day) or nicardipine (15 mg/kg/day). Simultaneous injection of the inhibitor of the synthesis of serotonin, p-chlorophenylalanine (200 mg/kg/day, i.p.), did not affect this attenuation of the isoprenaline-induced response. Similarly, the selective 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) or the 5-HT2 receptor antagonist, ketanserin, had no significant effect on the attenuation of isoprenaline-induced drinking behaviour. The inhibition of isoprenaline-induced drinking, was, however, effectively attenuated after treatment of the animals with 6-hydroxydopamine (2.5 micrograms) or clonidine (30 micrograms), injected intracerebroventricularly (i.c.v.). These results indicate that the calcium entry blockers accelerate the desensitization of central beta-adrenoceptors possibly by an action on central adrenoceptors of the rat.
Mustafa
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AA
Department of Medical Pharmacology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
D000433:1-Propanol / Q000494:pharmacology; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology; D004327:Drinking Behavior / Q000187:drug effects*; D010134:Fenclonine / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology*; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D009529:Nicardipine / Q000008:administration & dosage / Q000494:pharmacology; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology
D002121:Calcium Channel Blockers; D011943:Receptors, Adrenergic, beta; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; C020289:1-(2,5-dihydroxy-4-methylphenyl)-2-aminopropane; D016627:Oxidopamine; D000433:1-Propanol; D007650:Ketanserin; D014700:Verapamil; D009529:Nicardipine; D004110:Diltiazem; D009543:Nifedipine; D007545:Isoproterenol; D003000:Clonidine; D007099:Imipramine; D010134:Fenclonine