Assessment of the beta 2 adrenoceptor and Ca2+ channel-blocking activity of drugs with the rat portal vein.
The rat portal vein has spontaneous mechanical activity. The effects of beta-adrenoceptor agonists and antagonists and verapamil alone and together on this mechanical activity have been determined. Isoprenaline, but not dobutamine, attenuated the contractile activity. Three successive challenges to isoprenaline produced identical attenuation curves. The responses to isoprenaline were antagonized by propranolol, metoprolol, and ICI 118,551, and the pA2 values, derived by Schild analysis, were 9.12, 6.78, and 9.33, respectively. Thus, the rat portal vein contains predominantly beta 2-adrenoceptors. Verapamil attenuated the contractile activity of the rat portal vein, and this attenuation was not altered by the presence of propranolol at 10(-5) M. The potencies of isoprenaline and propranolol were not altered by the presence of a 30% attenuation of the contractile activity with verapamil at 10(-7) M. Thus, the rat portal vein may be used to determine the potencies of drugs as beta 2-adrenoceptor antagonists and as voltage dependent calcium channel blockers. In addition, the potency of drugs as beta 2-adrenoceptor antagonists on the rat portal vein may be determined in the presence of some voltage dependent calcium channel blockade.
Doggrell
S A
SA
Department of Pharmacology, School of Medicine, University of Auckland, New Zealand.
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism*; D004280:Dobutamine / Q000494:pharmacology; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D011169:Portal Vein / Q000187:drug effects* / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D004280:Dobutamine; C026777:ICI 118551; D011433:Propranolol; D014700:Verapamil; D008790:Metoprolol; D007545:Isoproterenol