Alpha 1-adrenoceptor subtype distribution and the coupling to phosphoinositide hydrolysis in rat and rabbit ventricular myocardium.
The relative contributions of the alpha 1A- and alpha 1B-adrenoceptor subtypes to the stimulation of phosphoinositide (PI) hydrolysis in rat and rabbit ventricular myocardium were defined pharmacologically using WB-4101 and chloroethylclonidine (CEC). Radioligand binding experiments with [3H]prazosin showed that the maximum number of alpha 1A-adrenoceptors in rat myocardium was about ten times higher than in rabbit myocardium. The proportion of the two [3H]prazosin binding sites with high and low affinity for WB-4101 was similar in the two species: approximately 30% of the alpha 1-adrenoceptor population was pharmacologically alpha 1A and approximately 70% was alpha 1B. Phenylephrine produced concentration-dependent stimulation of PI hydrolysis in rat ventricular strips as measured by [3H]inositol monophosphate accumulation, but this stimulation was much less in rabbit. In both of the two species, WB-4101 was very effective in inhibiting phenylephrine-stimulated PI hydrolysis, whereas CEC had a minimal effect. Altogether, the degree of PI hydrolysis appears to be determined by the density of myocardial alpha 1-adrenoceptors. However, despite the greater density of the alpha 1B-subtype, it is the alpha 1A-subtype that is mainly coupled to PI hydrolysis in mammalian myocardium.
Hattori
Y
Y
Department of Pharmacology, Hokkaido University School of Medicine Sapporo, Japan.
Nagashima
M
M
Akaishi
Y
Y
Kanno
M
M
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects / Q000648:ultrastructure; D006868:Hydrolysis; D007700:Kinetics; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011224:Prazosin / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification* / Q000378:metabolism*; D014316:Tritium
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D010716:Phosphatidylinositols; D018340:Receptors, Adrenergic, alpha-1; D014316:Tritium; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D018021:Lithium Chloride; D003000:Clonidine; D011224:Prazosin