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Mediation of most atypical effects by species homologues of the β 3 ‐adrenoceptor
Author(s) -
Blin Nathalie,
Nahmias Clara,
Drumare Marie F.,
Strosberg A. Donny
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13167.x
Subject(s) - pindolol , receptor , beta (programming language) , chinese hamster ovary cell , endocrinology , iodocyanopindolol , medicine , atenolol , intrinsic activity , partial agonist , biology , antagonist , adipose tissue , adrenergic receptor , pharmacology , agonist , propranolol , biochemistry , computer science , blood pressure , programming language
1 A wide panel of compounds acting on β‐adrenoceptors active either in mammalian heart or in rodent digestive tract and adipose tissues, were investigated for their effects on Chinese hamster ovary cells transfected with the human or murine β 3 ‐adrenoceptor gene. 2 The β 3 ‐agonists, bucindolol, CGP 12177A and pindolol exhibited the highest binding affinities; BRL 37344, LY 79771, ICI 201651 and SR 58611A presented high potencies in stimulating adenylyl cyclase; bupranolol appeared as the most efficient β 3 ‐antagonist. 3 This pharmacological analysis further established that the β 3 ‐adrenoceptor is the prototype of the adipose tissue atypical β‐adrenoceptor, since these receptors share a number of pharmacological properties which differ strikingly from those of β 1 ‐ and β 2 ‐adrenoceptors: low affinities for conventional β‐adrenoceptor agonists and antagonists, high potencies for novel compounds active in adipose tissues, partial agonistic activites for several β 1 /β 2 ‐antagonists. 4 Although the pharmacological profiles of the human and murine β 3 ‐receptor were very similar, some quantitative or even qualitative differences were observed for particular compounds such as propranolol, which exhibited weak and partial agonistic effects at the human β 3 ‐receptors and antagonistic effects at the murine β 3 ‐receptors. These differences may result from key amino‐acid substitutions between the human and the murine β 3 ‐receptor sequences, which may alter the binding site or signal processing. 5 Compounds active on atypical β‐sites of other tissues such as heart and digestive tract were also potent on the β 3 ‐adrenoceptor expressed in Chinese hamster ovary cells, suggesting that this receptor mediates most of the atypical properties described in various tissues, and that differences in ligand effects may result from tissue‐related specificities.