Dopaminergic suppression of pancreatic somatostatin secretion.
To characterize dopaminergic influences on pancreatic islet D cell function and its potential interaction with islet A and B cell function, the effect of dopamine (0.5-100 micro M) on immunoreactive somatostatin (IRS), insulin (IRI), and glucagon (IRG) release from rat islets incubated in vitro was studied. Dopamine significantly suppressed the release of IRS (P less than 0.001) and IRI (P less than 0.001) and augmented IRG release (P less than 0.001). Maximum suppression of IRS and IRI release was evident at 20 micro M dopamine with half-maximal suppression occurring at 0.5-1 micro M. Maximal stimulation of IRG release was observed at 100 micro M dopamine with a half-maximal response occurring at 5-10 micro M. Suppression of IRS secretion by dopamine (20 micro M) was completely reversed by the dopaminergic antagonists haloperidol (5 micro M) and pimozide (5 micro M) but was only partially reversed by the alpha adrenergic antagonist phentolamine (2 micro M), and was further suppressed by the beta adrenergic antagonist phentolamine (2 micro M). Suppression of IRI release by dopamine was completely reversed by propranolol, but was unaffected by haloperidol, pimozide, and phentolamine. There results indicate that dopamine directly affects pancreatic islet D cell function, and that islet B and D cells appear to be more sensitive to dopamine than are A cells. Dopamine suppresses IRS secretion predominantly through activation of dopaminergic receptors, whereas it suppresses IRI release through an alpha adrenergic mechanism and stimulates IRG release through a beta adrenergic mechanism.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D013004:Somatostatin / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D007328:Insulin; D011954:Receptors, Dopamine; D010868:Pimozide; D013004:Somatostatin; D005934:Glucagon; D011433:Propranolol; D006220:Haloperidol; D004298:Dopamine; D009638:Norepinephrine; D010646:Phentolamine