Muscarinic cholinergic stimulation of somatostatin secretion from long term dispersed cell cultures of fetal rat hypothalamus: inhibition by gamma-aminobutyric acid and serotonin.
Regulation of somatostatin (SS) secretion was studied in an in vitro system using collagenase-dispersed cells from fetal rat hypothalamus maintained in long term monolayer culture. Cultured cells exhibit a measurable basal secretion of immunoactive SS (SSLI) which can be augmented by carbachol, acetylcholine, or oxotremorine. The EC50 for carbachol is about 1 microM. Atropine, but not hexamethonium, antagonizes the action of cholinergic agonists. Cobalt or tetrodotoxin pretreatment diminishes basal secretion and eliminates the response to carbachol. Serotonin, several serotonin agonists, and gamma-aminobutyric acid (GABA) suppress carbachol-induced secretion. The GABA blockers bicuculline or picrotoxinin reverse the effect of added GABA and by themselves also augment SSLI secretion. Picrotin is inactive. The direct response to either bicuiculline or picrotoxinin is prevented by cobalt or tetrodotoxin treatment. These observations are consistent with the presence of a muscarinic cholinergic receptor which acts by a mechanism depending on an action potential and calcium influx to enhance the release of SSLI from neurosecretory cells. The data also support the conclusion that GABAergic transmission occurs within the cultures to tonically inhibit SSLI secretion. GABAergic, cholinergic, and serotoninergic systems may thus interact at the level of the hypothalamus to modulate SS secretion in vivo and thereby influence anterior pituitary release of GH and TSH.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D010095:Oxotremorine / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*; D013004:Somatostatin / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D006584:Hexamethonium Compounds; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D012701:Serotonin; D013779:Tetrodotoxin; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D010095:Oxotremorine; D001285:Atropine; D002217:Carbachol