D-2 dopamine receptor-mediated inhibition of adenylate cyclase activity in the intermediate lobe of the rat pituitary gland requires guanosine 5'-triphosphate.

After treatment with cholera toxin, homogenates of intact intermediate lobe (IL) tissue of rat pituitary gland synthesized more cAMP than did homogenates of untreated IL tissue, and only in the presence of GTP did dopamine or apomorphine diminish the elevated adenylate cyclase activity in homogenates of cholera toxin-treated IL tissue. Furthermore, when tested on cholera toxin-treated IL tissue, 5'-guanylyl imidodiphosphate [Gpp(NH)p] and two other nonhydrolyzable analogs of GTP inhibited adenylate cyclase activity in the absence of either a dopaminergic agonist or GTP; GTP reversed the Gpp(NH)p-induced inhibition of adenylate cyclase activity. Apomorphine, a dopaminergic agonist, abolished the ability of GTP to reverse the inhibition by Gpp(NH)p; this effect of apomorphine was prevented by fluphenazine, a dopaminergic antagonist. Sodium fluoride inhibited adenylate cyclase activity to approximately the same level obtained with GTP and apomorphine. In addition, apomorphine decreased cAMP accumulation and alpha MSH release from dispersed IL cells pretreated with cholera toxin.