Subtype selective regulation of coupling of rat cardiac beta adrenoceptors to adenylate cyclase.
There is now evidence from human studies to suggest that cardiac beta-adrenoceptor density and coupling to adenylate cyclase may be regulated in a subtype selective fashion. An animal model was used to investigate this further. Rats were infused for 6 days with the non-selective full agonist isoprenaline (n = 6) or the beta 1-selective partial agonist xamoterol (n = 6) with sham operated rats (n = 6) for control. beta-Adrenoceptor subtype density and coupling to adenylate cyclase were determined in left ventricular membranes. Isoprenaline infusion downregulated both beta 1- (30%) and beta 2- (63%) adrenoceptor subtypes with associated reduction in adenylate cyclase stimulation through both subtypes. Xamoterol did not downregulate either subtype, but selectively uncoupled beta 1-adrenoceptors. beta 1- and total beta-adrenoceptor-mediated stimulation of adenylate cyclase was reduced less by xamoterol than isoprenaline. We conclude that coupling of rat cardiac beta-adrenoceptors can be regulated in a subtype selective fashion and that the partial agonist xamoterol does not desensitise beta-adrenoceptor mediated stimulation of adenylate cyclase to the same extent as the full agonist isoprenaline.
Department of Clinical Pharmacology, Leicester Royal Infirmary, UK.
I R
IR
Arnold
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R
Mistry
D B
DB
Barnett
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D015536:Down-Regulation; D006801:Humans; D007262:Infusions, Intravenous; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D017307:Xamoterol / Q000008:administration & dosage / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D017307:Xamoterol; D000262:Adenylyl Cyclases; D007545:Isoproterenol