Characteristics of the beta-adrenergic stimulation of adenylate cyclase activity in rat ventral prostate and its modulation by androgens.
Beta-adrenergic agents cause a 2.5-3-fold stimulation of adenylate cyclase activity in rat ventral prostate membrane preparations with an order of potency (KD values) typical of a beta 2-subtype receptor: (-)isoproterenol (20 nM) greater than (-)epinephrine (70 nM) much greater than (-)norepinephrine (1 microM) much greater than dopamine (70 microM). The stimulatory effect exerted by high concentrations of dopamine (greater than 0.1 mM) is completely reversed by propranolol but not by haloperidol or sulpiride, thus indicating an action of dopamine mediated by the beta-adrenergic receptor. One week after castration, basal adenylate cyclase activity in prostatic membranes is 50% reduced. In the same group, the stimulation by isoproterenol is completely abolished in the absence of GTP, while the effect of GTP alone is reduced by 75%. The inhibitory effect of castration on basal as well as isoproterenol- and GTP-stimulated adenylate cyclase activity can be completely reversed by treatment of castrated animals with dihydrotestosterone, thus demonstrating the marked androgen dependency of adenylate cyclase activity in prostatic tissue. Since the response to direct stimulation of adenylate cyclase activity (assessed by NaF and forskolin) is only reduced by 33%-60% while the response to isoproterenol is 100% abolished, the present data indicates that the complete loss of beta-adrenergic responsiveness of prostatic adenylate cyclase following castration includes many steps, including those preceding adenylate cyclase activity, namely the beta-adrenergic receptor itself and/or its coupling via the GTP-binding protein. The large amplitude of the effects observed should facilitate study of the mechanisms involved in the marked regulation of the beta-adrenergic receptor-adenylate cyclase system by androgens in prostatic tissue.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology
D000728:Androgens; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D006160:Guanosine Triphosphate; D011433:Propranolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine