Article date: July 1994
By: Nathalie Blin, Clara Nahmias, Marie F. Drumare, A. Donny Strosberg, in Volume 112, Issue 3, pages 911-919
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 β3‐adrenoceptor gene.
The β3‐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 β3‐antagonist.
This pharmacological analysis further established that the β3‐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 β1‐ and β2‐adrenoceptors: low affinities for conventional β‐adrenoceptor agonists and antagonists, high potencies for novel compounds active in adipose tissues, partial agonistic activites for several β1/β2‐antagonists.
Although the pharmacological profiles of the human and murine β3‐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 β3‐receptors and antagonistic effects at the murine β3‐receptors. These differences may result from key amino‐acid substitutions between the human and the murine β3‐receptor sequences, which may alter the binding site or signal processing.
Compounds active on atypical β‐sites of other tissues such as heart and digestive tract were also potent on the β3‐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.
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 β3‐adrenoceptor gene.
The β3‐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 β3‐antagonist.
This pharmacological analysis further established that the β3‐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 β1‐ and β2‐adrenoceptors: low affinities for conventional β‐adrenoceptor agonists and antagonists, high potencies for novel compounds active in adipose tissues, partial agonistic activites for several β1/β2‐antagonists.
Although the pharmacological profiles of the human and murine β3‐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 β3‐receptors and antagonistic effects at the murine β3‐receptors. These differences may result from key amino‐acid substitutions between the human and the murine β3‐receptor sequences, which may alter the binding site or signal processing.
Compounds active on atypical β‐sites of other tissues such as heart and digestive tract were also potent on the β3‐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.
DOI: 10.1111/j.1476-5381.1994.tb13167.x
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