BRIEF COMMUNICATIONS Adenosine 3',5'-Cyclic-Monophosphate-Dependent Regulation of «i-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 ai-adrenergic receptor responsiveness. Experiments were performed in cultured rabbit aortic smooth muscle cells which were characterized previously according to a-adrenergic receptorbinding characteristics and receptor-coupled norepinephrine-stimulated Ca efflux. The addition of dibutyryl-cyclic adenosine monophosphate to the cell culture medium for 24 hours resulted in a concentration-related decrease in maximal [H]prazosin-binding capacity (41 ± 4% decrease with 1 mM dibutyryl-cyclic adenosine monophosphate) without an effect on [H]prazosin-binding affinity. Prostaglandin Ei (10 HM) and forskolin (10 /IM) caused similar decreases in maximal [H]prazosin-binding capacity, whereas butyrate (1 ITIM) and dibutyryl-guanosine-3',5' cyclicmonophosphate (1 ITIM) had no effect. Dibutyryl-cyclic adenosine monophosphate (1 ITIM) caused significant potentiation of the decrease in [H]prazosin-binding caused by a submaximal (10 riM) but not a maximal (10 MM) concentration of norepinephrine, suggesting that cyclic adenosine monophosphate may act at a distal step in common with norepinephrine to reduce a-adrenergic receptor number. Despite the approximately 41% reduction in a-adrenergic receptor number following 24-hour incubation of cells with dibutvryl-cyclic adenosine monophosphate, maximal norepinephrine-stimulated Ca efflux was not reduced, consistent with the markedly nonlinear relationship between a-adrenergic receptor occupancy and maximal norepinephrine-stimulated Ca 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 aadrenergk responsiveness in vascular smooth muscle. (Circ Res 58: 292-297, 1986)