Inhibitory effect of nociceptin on somatostatin secretion of the isolated perfused rat stomach.
The heptadecapeptide nociceptin/orphanin FQ (N/OFQ) has recently been isolated from porcine and rat brain and identified as the endogenous ligand of the N/OFQ receptor (NOP). It shows structural similarity with opioid peptides. N/OFQ has also been demonstrated in the gastrointestinal tract, where it inhibits gastrointestinal motility. The effect of N/OFQ on gastric neuroendocrine function is unknown as yet. In the isolated perfused rat stomach, N/OFQ 10(-6) M shows a small, but not significant decrease of basal somatostatin (SRIF) secretion. At the doses of 10(-12) M, 10(-10) and 10(-8) M N/OFQ has neither an effect on basal SRIF nor on basal vasoactive intestinal polypeptide (VIP), gastrin, substance P or bombesin secretion, respectively. However, gastric inhibitory polypeptide (GIP) 10(-9) M prestimulated SRIF secretion is significantly inhibited by N/OFQ 10(-8) M (-45+/-11%; p<0.05 vs. GIP). During concomitant infusion of the specific competitive NOP receptor antagonist [Nphe(1)]nociceptin(1-13)NH(2) 10(-6) M, the effect of N/OFQ is abolished (6+/-11%; p<0.05 vs. GIP and N/OFQ) while the opiate receptor antagonist naloxone 10(-6) M has no significant effect (-32+/-9%; ns vs. GIP and N/OFQ). At the higher concentration of N/OFQ 10(-6) M, the inhibition of prestimulated SRIF secretion (-58+/-6%; p<0.05 vs. GIP) is not influenced by the NOP receptor antagonist at the concentration of 10(-6) M (-49+/-9%; ns vs. GIP and N/OFQ) and 10(-5) M (-69+/-10%; ns vs. GIP and N/OFQ), respectively. On the other hand, infusion of naloxone 10(-6) M attenuates the inhibitory effect of N/OFQ 10(-6) M significantly (-21+/-6%; p<0.05 vs. GIP and N/OFQ).Thus, N/OFQ is an inhibitor of gastric somatostatin secretion. At the lower dose, this effect is transmitted via NOP receptors, while at the higher dose of 10(-6) M, the effect is at least in part mediated via opiate receptors.
Department of Internal Medicine II, Technical University of Munich, Ismaningerstr. 22, 81675, Munich, Germany. florian.lipple@lrz.tum.de
Florian
F
Lippl
Volker
V
Schusdziarra
Kerstin
K
Huepgens
Hans Dieter
HD
Allescher
D000818:Animals; D001839:Bombesin / Q000378:metabolism; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists; D012636:Secretory Rate / Q000187:drug effects; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000378:metabolism*; D013270:Stomach / Q000187:drug effects*; D013373:Substance P / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism; D000097629:Nociceptin
D001839:Bombesin; D005749:Gastric Inhibitory Polypeptide; D005755:Gastrins; D009270:Naloxone; D018847:Opioid Peptides; D011957:Receptors, Opioid; D013004:Somatostatin; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D000097629:Nociceptin