[Stimulation of adenylate cyclase by the isoforms of human and rat beta-3 adrenergic receptor expressed in the CHO cells].
OBJECTIVE
The beta 3 adrenergic receptor stimulates lipolysis and colonic relaxation in the rat, and, suggestively, in man. Several human forms generated by different mRNA splicings can occur: the A form of 396 amino acids and the B and C forms extended by 12 and 6 amino acids respectively, in the C-terminus region. In order to characterize these different forms as expressed in CHO cells, we studied adenylyl cyclase stimulation by the beta 3 agonists, SR58611A and BRL37344 and its inhibition by the beta 3 antagonist SR59230.


RESULTS
This antagonist totally inhibited SR58611-adenylyl cyclase stimulation with the following hierarchy of potency: C form >> B > A. In rat, a unique form is expressed which is close to the human B form. This form was the less sensitive to beta 1 and beta 2 antagonists.


CONCLUSIONS
These findings constitute a molecular pharmacological basis for the design of beta 3 agonists of therapeutic value.
Unité INSERM 10, Hôpital Bichat-Claude Bernard, Paris.
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Levasseur
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Pigeon
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Reyl-Desmars
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Caput
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Lewin
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006224:Cricetinae; D003864:Depression, Chemical; D004983:Ethanolamines / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D013268:Stimulation, Chemical
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011412:Propanolamines; C026777:ICI 118551; C057368:BRL 37344; D000262:Adenylyl Cyclases; D007545:Isoproterenol
Stimulation de l'adénylate cyclase par les isoformes de récepteur beta 3 adrénergique humain et de rat exprimés dans la cellule CHO.