Abstract
Despite their opposite effects on prolactin secretion, both dopamine and angiotensin II inhibit adenylate cyclase activity in homogenates of anterior pituitary cells in primary culture. Dopamine and angiotensin II inhibition of adenylate cyclase was not additive, suggesting that both neurohormones inhibit the adenylate cyclase of the lactotroph cells. Pretreatment with Bordetella pertussis toxin (islet activator protein) completely suppressed the dopamine-induced inhibition of both adenylate cyclase and prolactin secretion. The islet activator protein also reversed the angiotensin II-induced inhibition of the adenylate cyclase activity. In contrast, angiotensin II stimulation of prolactin release was not affected by the toxin. Angiotensin II also induced a dose-dependent stimulation of inositol phosphates (250%) with an EC50 of 0.1 nM, close to that observed for prolactin secretion. Islet activator protein pretreatment did not block the stimulation of inositol phosphate production. Dopamine inhibited the angiotensin II-stimulated prolactin release and the production of inositol phosphates induced by angiotensin II. It is concluded that angiotensin II and dopamine receptors of lactotroph cells are able to modulate both cAMP and inositol phosphate production. The dopamine receptor of lactotrophs appears to be the first example of a receptor which is negatively coupled to the production of inositol phosphates.
Highlights
Despite their opposite effects on prolactin secretion, detellu pertussis, named islet activating protein (IAPl), both dopamine and angiotensin I1 inhibit adenylate which is known to suppress negative coupling of receptors to cyclase activity in homogenates of anterior pituitary adenylate cyclase, has been shown to block the dopaminecells in primaryculture
Angiotensin I1 Recently we have found that AI1 is more potent than stimulation of prolactin release wansot affected by the dopamine in inhibiting anterior pituitary adenylate cyclase toxin
0.1 nM, close to that observed for prolactin secretion. and dopamine have opposite effects on prolactin secretion, Islet activator protein pretreatment did not block the the former stimulates (18,19),whereas the latter inhibits the stimulation of inositol phosphate production
Summary
From the $Unite159, Institute National dela Sante etde la Recherche Medicale, 2 ter, rued’A&sia, 75014 Paris, France, the $Centre Nationale dela Recherche Scientifique-Znstitute National dlea Sante et dela Recherche Medicale de PhnrmacologieEndocrinologie,B.P. 5055 rue de la Cardonille 34033 Montpellier, France, andthe TDepartamento deBioenergetica, Centro de Znvestigaewnes e n Fisiologica Celular, Universidad Nacional Autonoma de Mexico0,4510, Mexico D.F., Mexico Despite their opposite effects on prolactin secretion, detellu pertussis, named islet activating protein (IAPl), both dopamine and angiotensin I1 inhibit adenylate which is known to suppress negative coupling of receptors to cyclase activity in homogenates of anterior pituitary adenylate cyclase, has been shown to block the dopaminecells in primaryculture. It is likely that dopamine reduces prolactin secretion by directly inhibiting adenylate cyclase activity of lactotroph cells (913) In accordance with this hypothesis, the toxin from Bordecapitation of female rats (200-230 g, Sprague-Dawley, Charles Rivers Breeding Laboratories, St. Aubinles Elbeuf, France). ‘The abbreviations used are: IAP, islet activator protein; AII, angiotensin 11; InsP, inositol phosphate; InsP,, InsP2, and Imp, inositol tri-, di-, and monophosphate; DMEM, Dulbecco’s modified Eagle’s medium
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