ABSTRACT
5-Hydroxy-2-aminotetralin derivatives in which one N-alkyl substituent carries a functional group have been prepared and their dopaminergic activities compared with those of 5-hydroxy-2-(di-n-propylamino)tetralin (5-OH-DPAT) and known ergolines. Several members of the series demonstrated high affinities in dopamine (DA) receptor binding and DA agonist properties in the rotational behavior model in the range of known potent ergolines. The results suggest that the accessory binding site for the larger N-alkyl substituent of the 5-hydroxy-2-aminotetralins can accommodate various neutral and bulky functionalities and is probably identical with the site(s) to which the 8-substituents of the ergolines bind.
Subject(s)
Naphthalenes/pharmacology , Receptors, Dopamine/drug effects , Tetrahydronaphthalenes/pharmacology , Animals , Antiparkinson Agents/pharmacology , Binding Sites , Cattle , In Vitro Techniques , Rats , Structure-Activity RelationshipABSTRACT
Highly selective beta-adrenoceptor blocking agents with a beta 1: beta 2-selectivity ratio of 0.015 to 3400 were used to characterize the beta-adrenoceptors present in rat kidney and to identify those mediating renin release. The results obtained with ICYP binding to kidney membranes revealed the presence of both beta 1- and beta 2-adrenoceptors in a ratio of 1:1. The pKD beta 1- and pKD beta 2-values of selective beta-antagonists obtained in rat kidney membranes correlated well with those found in guinea pig left ventricle (beta 1) and lung (beta 2), indicating that kidney receptor subtypes are pharmacologically identical with those in the ventricle and lung, respectively. In the isolated perfused rat kidney, the apparent pA2 values of beta 1-selective blockers for inhibition of isoprenaline-stimulated renin release correlated well with pKD beta 1, but not with pKD beta 2 values. These results clearly show that the beta 1-adrenoceptor subtype mediates renin release in the rat kidney.
