Mechanisms of somatostatin action in pituitary cells.
We have examined the mechanisms by which S-14 inhibits pituitary hormone secretion in a homogeneous cell population: the clonal GH4C1 cell line. The S-14 receptor in GH4C1 cells is coupled to Ni, a guanine nucleotide binding protein which mediates S-14-induced inhibition of VIP-stimulated adenylate cyclase activity, cyclic AMP production and hormone secretion. In addition, a functional Ni is required for S-14 to inhibit basal hormone secretion, an action which appears to be independent of cyclic AMP concentrations. Accumulating evidence indicates that the mechanism of S-14 action in somatotrophs is similar to that in GH4C1 cells. Although S-14 consistently inhibits basal GH secretion, its effects on basal cyclic AMP levels in normal pituitary cells are variable and often not significant (10-14). In contrast, S-14 inhibits prostaglandin and growth hormone releasing factor (GRF) stimulated cyclic AMP accumulation and GH release in parallel. Furthermore, S-14 partially blocks prostaglandin and GRF stimulation of adenylate cyclase activity in rat anterior pituitary membranes. Finally, pretreatment of primary cultures of rat pituitary cells with IAP antagonizes S-14 inhibition of both basal and GRF-stimulated GH release.
Schonbrunn
A
A
Dorflinger
L J
LJ
Koch
B D
BD
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D005576:Colforsin; D000242:Cyclic AMP / Q000502:physiology; D004224:Diterpenes / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D006160:Guanosine Triphosphate / Q000502:physiology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D010902:Pituitary Gland / Q000502:physiology*; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology*; D017481:Receptors, Somatostatin; D012636:Secretory Rate / Q000187:drug effects; D013004:Somatostatin / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors
D004224:Diterpenes; D011956:Receptors, Cell Surface; D017481:Receptors, Somatostatin; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D006165:Guanylyl Imidodiphosphate; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D006160:Guanosine Triphosphate; D011388:Prolactin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases