Secretion of ghrelin from rat stomach ghrelin cells in response to local microinfusion of candidate messenger compounds: a microdialysis study.
Ghrelin is produced by A-like cells (ghrelin cells) in the mucosa of the acid-producing part of the stomach. The mobilization of ghrelin is stimulated by nutritional deficiency and suppressed by nutritional abundance. In an attempt to identify neurotransmitters and regulatory peptides that may contribute to the physiological, nutrient-related regulation of ghrelin secretion, we challenged the ghrelin cells in situ with a wide variety of candidate messengers, including known neurotransmitters (e.g. acetylcholine, catecholamines), candidate neurotransmitters (e.g. neuropeptides), local tissue hormones (e.g. serotonin, histamine, bradykinin, endothelin), circulating gut hormones (e.g. gastrin, CCK, GIP, neurotensin, PYY, secretin) and other circulating hormones/regulatory peptides (e.g. calcitonin, glucagon, insulin, PTH). Microdialysis probes were placed in the submucosa of the acid-producing part of the rat stomach. Three days later, the putative messenger compounds were administered via the microdialysis probe (reverse microdialysis) at a screening dose of 0.1 mmol l(-1) for regulatory peptides and 0.1 and 1 mmol l(-1) for amines and amino acids. The rats were awake during the experiments. The resulting microdialysate ghrelin concentration was monitored continuously for 3 h (radioimmunoassay), thereby revealing stimulators or inhibitors of ghrelin secretion. Dose-response curves were constructed for each candidate messenger that significantly (p<0.05) affected ghrelin mobilization at the screening dose. Peptides that showed a (non-significant) tendency to affect ghrelin release at the screening dose were also given at a dose of 0.3 or 1 mmol l(-1). Adrenaline, noradrenaline, endothelin and secretin stimulated ghrelin release, while somatostatin and GRP inhibited. Whether these agents act directly or indirectly on the ghrelin cells remains to be investigated. All other candidate messengers were without measurable effects, including acetylcholine, serotonin, histamine, GABA, aspartic acid, glutamic acid, glycine, VIP, PACAP, CGRP, substance P, NPY, PYY, PP, gastrin, CCK, GIP, insulin, glucagon, GLP and glucose.
de la Cour
Charlotta Dornonville
CD
Unit of Cellular and Molecular Pharmacology, Dept of Exp. Med, University of Lund, BMC F13, S-221 84 Lund, Sweden. CDDC@novonordisk.com
Norlén
Per
P
Håkanson
Rolf
R
D000588:Amines / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism*; D005755:Gastrins / Q000494:pharmacology; D005768:Gastrointestinal Hormones / Q000494:pharmacology; D054439:Ghrelin; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D017551:Microdialysis / Q000379:methods*; D009479:Neuropeptides / Q000494:pharmacology; D010187:Pancreatic Hormones / Q000494:pharmacology; D036361:Peptide Hormones / Q000378:metabolism*; D019894:Peptide YY / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000166:cytology / Q000187:drug effects
D000588:Amines; D000596:Amino Acids; D005755:Gastrins; D005768:Gastrointestinal Hormones; D054439:Ghrelin; D007328:Insulin; D009479:Neuropeptides; D010187:Pancreatic Hormones; D036361:Peptide Hormones; D019894:Peptide YY; D005749:Gastric Inhibitory Polypeptide; D006632:Histamine; D005934:Glucagon; D005947:Glucose