Evidence That the D-2 Dopamine Receptor in the Intermediate Lobe of the Rat Pituitary Gland Is Associated with an Inhibitory Guanyl Nucleotide Component
Stimulation of the D-2 dopamine receptor in the intermediate lobe (IL) of the rat pituitary gland diminishes both basal and isoproterenol-stimulated adenylate cyclase activity. Cholera toxin increases IL adenylate cyclase activity and reduces the ability of beta-adrenergic agonists to further enhance enzyme activity but does not alter the functioning of the D-2 dopamine receptor. Indeed, cholera toxin-treated IL tissue provides a useful experimental system to investigate the involvement of guanyl nucleotides in the functioning of the IL D-2 dopamine receptor. GTP is obligatory for dopaminergic agonists to inhibit adenylate cyclase activity of cholera toxin-treated IL tissue. Furthermore, 5′-guanylyl imidodiphosphate (Gpp[NH]p), a nonhydrolyzable analog of GTP, inhibits adenylate cyclase activity in the absence of a dopaminergic agonist. GTP reverses the Gpp(NH)p-induced inhibition of adenylate cyclase activity; apomorphine, a dopaminergic agonist, abolishes this effect of GTP. It is hypothesized that the D-2 dopamine receptor in the IL interacts with an inhibitory guanyl nucleotide component (Ni); stimulation of the D-2 dopamine receptor alters the properties of Ni so that Ni can interact with GTP and inhibit adenylate cyclase activity.
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