Relaxation by vasoactive intestinal polypeptide in the gastric fundus of nitric oxide synthase-deficient mice.
In many gastrointestinal tissues nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) both play a role as inhibitory non-adrenergic non-cholinergic neurotransmitters. As the mode of interaction between NO and VIP remains controversial, the aim of this study was to investigate the interplay between NO and VIP in the mouse gastric fundus and to evaluate the nitric oxide synthase (NOS) isoform involved in VIP-induced relaxation by using inducible NOS (iNOS), endothelial NOS (eNOS) and neuronal NOS (nNOS) knockout mice. The influence of NOS inhibitors on the relaxant effect of VIP was determined in isolated smooth muscle cells and smooth muscle strips of wild-type and knockout mice. In isolated smooth muscle cells from wild-type, eNOS knockout and nNOS knockout mice, the relaxation induced by VIP (10(-9) M) was inhibited by approximately 70-95 % by both the non-selective NOS inhibitor N(G)-nitro-L-arginine (L-NA; 10(-4) M) and the selective inducible NOS inhibitor N-(3-(aminomethyl)-benzyl)acetamidine (1400W; 10(-6) M). In cells isolated from iNOS knockout mice, VIP still induced full relaxation but it was not influenced by L-NA or 1400W. In smooth muscle strips from wild-type and knockout mice, the concentration-dependent relaxation by VIP (10(-9) to 3 x 10(-7) M) was not influenced by L-NA or 1400W. These results suggest that the experimental method determines the influence of NOS inhibitors on the relaxant effect of VIP. iNOS, probably induced by the isolation procedure, might be involved in the relaxant effect of VIP in isolated smooth muscle cells but not in classic smooth muscle strips.
Dick
Joëlle M C
JM
Heymans Institute of Pharmacology, Faculty of Medicine and Health Sciences, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
Van Molle
Wim
W
Brouckaert
Peter
P
Lefebvre
Romain A
RA
D000818:Animals; D005748:Gastric Fundus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D014660:Vasoactive Intestinal Peptide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse