Human pancreatic tumor growth hormone-releasing factor stimulates anterior pituitary adenylate cyclase activity, adenosine 3',5'-monophosphate accumulation, and growth hormone release in a calmodulin-dependent manner.
Pituitary GH secretion is regulated by Ca+2 and cAMP. We show that human pancreatic tumor GRF (hpGRF) stimulates anterior pituitary adenylate cyclase activity, cAMP accumulation, and GH release. The relationship between Ca+2 and the stimulating effects of the Ca+2 ionophore A23187 on cAMP accumulation and GH release in vitro was studied. To evaluate the role of the Ca+2-binding protein calmodulin in this system, we used the calmodulin antagonist W7, a naphthalene-sulfonamide derivative, and its less active analog W5. W7 inhibited hpGRF-stimulated adenylate cyclase activity, cAMP accumulation, and GH release, whereas W5 was either poorly effective or ineffective. Somatostatin (SRIF) also attenuated hpGRF stimulation of adenylate cyclase. These results suggest that the actions of Ca+2-calmodulin and cAMP are interrelated in modulating GH release. Calmodulin participates in hpGRF stimulation of adenylate cyclase, cAMP formation, and GH release. The attenuation of hpGRF-stimulated adenylate cyclase activity by SRIF may be one of the mechanisms for its GH inhibitory action.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002147:Calmodulin / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D002147:Calmodulin; D010446:Peptide Fragments; D013449:Sulfonamides; C036893:somatotropin releasing factor 40; D000001:Calcimycin; D013004:Somatostatin; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D000242:Cyclic AMP; D000262:Adenylyl Cyclases