Influence of vasoactive intestinal polypeptide and NG-nitro-L-arginine methyl ester on cholinergic neurotransmission in the rat gastric fundus.
The possible modulating effect of vasoactive intestinal polypeptide (VIP) and nitric oxide (NO), on cholinergic neurotransmission was assessed in longitudinal muscle strips of rat gastric fundus. VIP and NO are the putative co-transmitters of the inhibitory non-adrenergic non-cholinergic (NANC) neurones in this tissue. VIP concentration dependently inhibited cholinergic contractions induced by 2-min transmural stimulation, relaxed tissues, the tone of which was continuously raised by transmural stimulation, and shifted to the right the frequency-response curves for contraction induced by transmural stimulation with a cumulative increase of frequency. The same effect was found when contractions were induced with methacholine, suggesting that only functional antagonism at the postsynaptic smooth muscle cell level is involved. On 30-min incubations, 3 x 10(-4) M NG-nitro-L-arginine methyl ester (L-NAME) potentiated cholinergic responses to 20-s transmural stimulation, while not influencing contractions of similar amplitude evoked by methacholine; the cholinergic responses to 2-min transmural stimulation were also not influenced. The potentiating effect of L-NAME was prevented by L-arginine but not D-arginine. These results suggest that endogenous NO released from the inhibitory NANC neurones during short trains of transmural stimulation interferes with cholinergic neurotransmission either by functional antagonism of acetylcholine at the postsynaptic level or by presynaptic inhibition of acetylcholine release.
Lefebvre
R A
RA
Heymans Institute of Pharmacology, University of Gent Medical School, Belgium.
De Vriese
A
A
Smits
G J
GJ
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D005748:Gastric Fundus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D016210:Methacholine Chloride; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D001120:Arginine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester