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.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D010902:Pituitary Gland / Q000378:metabolism*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism
D006150:Guanine Nucleotides; D011943:Receptors, Adrenergic, beta; D011954:Receptors, Dopamine; D006165:Guanylyl Imidodiphosphate; D013134:Spiperone; D006160:Guanosine Triphosphate; D002772:Cholera Toxin; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D001058:Apomorphine