Adenosine 3',5'-cyclic-monophosphate-dependent regulation of alpha 1-adrenergic receptor number in rabbit aortic smooth muscle cells.
The purpose of this study was to determine whether a cyclic adenosine 3',5'-monophosphate-dependent process can be involved in the regulation of vascular smooth muscle alpha 1-adrenergic receptor responsiveness. Experiments were performed in cultured rabbit aortic smooth muscle cells which were characterized previously according to alpha-adrenergic receptor-binding characteristics and receptor-coupled norepinephrine-stimulated 45Ca++ efflux. The addition of dibutyryl-cyclic adenosine monophosphate to the cell culture medium for 24 hours resulted in a concentration-related decrease in maximal [3H]prazosin-binding capacity (41 +/- 4% decrease with 1 mM dibutyryl-cyclic adenosine monophosphate) without an effect on [3H]prazosin-binding affinity. Prostaglandin E1 (10 microM) and forskolin (10 microM) caused similar decreases in maximal [3H]prazosin-binding capacity, whereas butyrate (1 mM) and dibutyryl-guanosine-3',5' cyclic-monophosphate (1 mM) had no effect. Dibutyryl-cyclic adenosine monophosphate (1 mM) caused significant potentiation of the decrease in [3H]prazosin-binding caused by a submaximal (10 nM) but not a maximal (10 microM) concentration of norepinephrine, suggesting that cyclic adenosine monophosphate may act at a distal step in common with norepinephrine to reduce alpha-adrenergic receptor number. Despite the approximately 41% reduction in alpha-adrenergic receptor number following 24-hour incubation of cells with dibutyryl-cyclic adenosine monophosphate, maximal norepinephrine-stimulated 45Ca++ efflux was not reduced, consistent with the markedly nonlinear relationship between alpha-adrenergic receptor occupancy and maximal norepinephrine-stimulated 45Ca++ efflux in this cell system. These data provide evidence for a novel mechanism by which hormones or drugs which increase cyclic adenosine monophosphate levels can modulate alpha-adrenergic responsiveness in vascular smooth muscle.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology; D002118:Calcium / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000648:ultrastructure*; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D014316:Tritium
D011942:Receptors, Adrenergic, alpha; D014316:Tritium; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000527:Alprostadil; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin