title: Gastric inhibitory polypeptide stimulates glucocorticoid secretion in rats, acting through specific receptors coupled with the adenylate cyclase-dependent signaling pathway.
abstract: Gastric inhibitory polypeptide (GIP) is a 42-amino acid peptide, belonging to the VIP-secretin-glucagon superfamily, some members of this group are able to regulate adrenocortical function. GIP-receptor mRNA has been detected in the rat adrenal cortex, but investigations on the effect of GIP on steroid-hormone secretion in this species are lacking. Hence, we have investigated the distribution of GIP binding sites in the rat adrenal gland and the effect of their activation in vivo and in vitro. Autoradiography evidenced abundant [125I]GIP binding sites exclusively in the inner adrenocortical layers, and the computer-assisted densitometric analysis of autoradiograms demonstrated that binding was displaced by cold GIP, but not by either ACTH or the selective ACTH-receptor antagonist corticotropin-inhibiting peptide (CIP). The intraperitoneal (IP) injection of GIP dose-dependently raised corticosterone, but not aldosterone plasma concentration: the maximal effective dose (10 nmol/rat) elicited a twofold increase. GIP did not affect aldosterone and cyclic-AMP release by dispersed zona glomerulosa cells. In contrast, GIP enhanced basal corticosterone secretion and cyclic-AMP release by dispersed inner adrenocortical cells in a concentration-dependent manner, and the maximal effective concentration (10(-7) M) evoked 1.5- and 2.4-fold rises in corticosterone and cyclic-AMP production, respectively. GIP (10(-7) M) did not display any additive or potentiating effect on corticosterone and cyclic-AMP responses to submaximal or maximal effective concentrations of ACTH. The corticosterone secretagogue action of 10(-7) M GIP was abolished by the protein kinase A (PKA) inhibitor H-89 (10(-5)M), and unaffected by CIP (10(-6)M). Collectively, these findings indicate that GIP exerts a moderate but statistically significant stimulatory effect on basal glucocorticoid secretion in rats, acting through specific receptors coupled with the adenylate cyclase/PKA-dependent signaling pathway.
authors.affiliation: Department of Human Anatomy and Physiology, University of Padua, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Mazzocchi
authors.forename: P
authors.initials: P
authors.lastname: Rebuffat
authors.forename: V
authors.initials: V
authors.lastname: Meneghelli
authors.forename: L K
authors.initials: LK
authors.lastname: Malendowicz
authors.forename: C
authors.initials: C
authors.lastname: Tortorella
authors.forename: G
authors.initials: G
authors.lastname: Gottardo
authors.forename: G G
authors.initials: GG
authors.lastname: Nussdorfer
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000302:Adrenal Cortex / Q000187:drug effects*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000097:blood; D000818:Animals; D002469:Cell Separation; D003345:Corticosterone / Q000097:blood; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism / Q000494:pharmacology*; D005938:Glucocorticoids / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D018043:Receptors, Corticotropin / Q000037:antagonists & inhibitors; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism*; D015398:Signal Transduction; D013449:Sulfonamides
chemical_list: D005938:Glucocorticoids; D007546:Isoquinolines; D010446:Peptide Fragments; D018043:Receptors, Corticotropin; D011964:Receptors, Gastrointestinal Hormone; D013449:Sulfonamides; D000450:Aldosterone; D005749:Gastric Inhibitory Polypeptide; C026034:ACTH (7-38); D000324:Adrenocorticotropic Hormone; C041086:gastric inhibitory polypeptide receptor; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D003345:Corticosterone