Modulation of nitrergic relaxant responses by peptides in the mouse gastric fundus.
The effects of pituitary adenylate cyclase-activating peptide (PACAP-38) and vasoactive intestinal polypeptide (VIP) were investigated in the gastric fundus strips of the mouse. In carbachol (CCh) precontracted strips, in the presence of guanethidine, electrical field stimulation (EFS) elicited a fast inhibitory response that may be followed, at the highest stimulation frequencies employed, by a sustained relaxation. The fast response was abolished by the nitric oxide (NO) synthesis inhibitor L-N(G)-nitro arginine (L-NNA) or by the guanylate cyclase inhibitor (ODQ), the sustained one by alpha-chymotrypsin. alpha-Chymotrypsin also increased the amplitude of the EFS-induced fast relaxation. PACAP-38 and VIP caused tetrodotoxin-insensitive sustained relaxant responses that were both abolished by alpha-chymotrypsin. Apamin did not influence relaxant responses to EFS nor relaxation to both peptides. PACAP 6-38 abolished EFS-induced sustained relaxations, increased the amplitude of the fast ones and antagonized the smooth muscle relaxation to both PACAP-38 and VIP. VIP 10-28 and [D-p-Cl-Phe6,Leu17]-VIP did not influence the amplitude of both the fast or the sustained response to EFS nor influenced the relaxation to VIP and PACAP-38. The results indicate that in strips from mouse gastric fundus peptides, other than being responsible for EFS-induced sustained relaxation, also exerts a modulatory action on the release of the neurotransmitter responsible for the fast relaxant response, that appears to be NO.
Baccari
M C
MC
Department of Physiology, University of Florence, Viale G.B. Morgagni 63, 50134, Florence, Italy. mcaterina.baccari@unifi.it
Calamai
F
F
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D002918:Chymotrypsin / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005748:Gastric Fundus / Q000187:drug effects / Q000502:physiology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000494:pharmacology*; D019335:Nitroarginine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011810:Quinoxalines / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; C495402:Adcyap1 protein, mouse; D018679:Cholinergic Agonists; D004791:Enzyme Inhibitors; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D010069:Oxadiazoles; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011810:Quinoxalines; C075647:pituitary adenylate-cyclase-activating-peptide (6-38); D019335:Nitroarginine; D001030:Apamin; D014660:Vasoactive Intestinal Peptide; C047945:vasoactive intestinal peptide (10-28); D002217:Carbachol; D002918:Chymotrypsin; C117608:alpha-chymotrypsin; D006162:Guanylate Cyclase