title: Somatostatin and muscarinic inhibition of canine enteric endocrine cells: cellular mechanisms.
abstract: Using a recently developed canine primary enteric endocrine cell culture system, we have investigated the role of adenosine 3',5'-cyclic monophosphate (cAMP) in mediating the release of neurotensin and enteroglucagon. Epinephrine-stimulated peptide release was concomitant with an increase in cAMP accumulation. Carbachol and somatostatin (SRIF) markedly inhibited the epinephrine effect on both peptide release and cAMP content. The addition of 3-isobutyl-1-methylxanthine potentiated epinephrine-stimulated peptide release without altering the relative inhibition by carbachol and SRIF, suggesting that these agents did not inhibit endocrine cell function by increasing phosphodiesterase activity. To determine the role of cAMP production in mediating inhibition of peptide release, cells were incubated with the bacterial toxin, pertussis toxin (PT). In cultures pretreated with PT, carbachol inhibition of both peptide release and cAMP accumulation was completely reversed. In contrast, SRIF inhibition of cAMP content was completely reversed after PT treatment, but inhibition of peptide release was only partially reversed. Additionally, toxin treatment only partially reversed SRIF inhibition of forskolin- and calcium ionophore-stimulated peptide release. These data suggest that muscarinic cholinergic inhibition of neurotensin and enteroglucagon release is mediated entirely through the guanine nucleotide-binding protein (Ni) or a similar toxin-sensitive, GTP-binding protein. SRIF-inhibited peptide release is mediated partially through a toxin-sensitive substrate, as evidenced by PT reversal of reduced cAMP levels. SRIF may also inhibit neurotensin and enteroglucagon release by a cAMP-independent pathway that is not coupled to Ni or a similar PT-sensitive, GTP-binding protein.
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D004763:Glucagon-Like Peptides / Q000378:metabolism*; D007082:Ileum / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism*; D037342:Pertussis Toxin; D011976:Receptors, Muscarinic / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D005768:Gastrointestinal Hormones; D011976:Receptors, Muscarinic; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000001:Calcimycin; D009496:Neurotensin; D013004:Somatostatin; D004763:Glucagon-Like Peptides; D003994:Bucladesine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D015056:1-Methyl-3-isobutylxanthine; D004837:Epinephrine