Stimulation of nitric oxide from muscle cells by VIP: prejunctional enhancement of VIP release

Abstract

The source of nitric oxide (NO) and its role in neurally induced relaxation was examined in smooth muscle of the stomach and tenia coli. Field stimulation of gastric muscle strips was accompanied by frequency-dependent relaxation, vasoactive intestinal peptide (VIP) release, and NO production: the NO synthase inhibitor, NG-nitro-L-arginine (L-NNA) completely inhibited NO production and partly inhibited VIP release (52-54%) and relaxation (58-88%); inhibition of all three functions was reversed by L-arginine but not by D-arginine. In isolated gastric muscle cells, VIP caused relaxation and stimulated NO production: L-NNA completely inhibited NO production and partly inhibited relaxation; the inhibition was reversed by L-arginine but not by D-arginine. Abolition of NO production with only partial inhibition of relaxation implied that NO production from muscle cells induced by the action of VIP was partly responsible for relaxation. By contrast, field stimulation of tenia coli was accompanied by relaxation and VIP release but not by NO production. Neither VIP release nor relaxation was affected by L-NNA. In isolated muscle cells of tenia coli, VIP caused relaxation but did not stimulate NO production; relaxation in these cells was not affected by L-NNA. We conclude that 1) VIP is the primary relaxant transmitter in both gastric muscle and tenia coli, 2) the release of VIP in gastric muscle but not in tenia coli stimulates NO production from target muscle cells, and 3) NO amplifies the relaxant effect of VIP in muscle cells and acts presynaptically to enhance the release of VIP.

Nitric oxide, and not vasoactive intestinal peptide, as the main neurotransmitter of vagally induced relaxation of the guinea pig stomach

“…The most important evidence that VIP does not act through NO is that L-NAME prevented relaxations induced by vagal stimulation but did not affect those induced by VIP. Thus, even if VIP is released by vagal stimulation, it does not act through stimulation of NO production from neurones or smooth muscle cells, as has been suggested (Grider et al, 1992). This would hold even if these tissues contain isoforms of NOS not detected by our antibody staining.…”

“…For instance, electrical field stimulation of muscle strips from the guineapig and rat gastric fundus causes release of VIP-like immunoreactivity (Grider & Makhlouf, 1987;D'Amato et al, 1992). It has also been suggested that VIP and NO are co-transmitters of gastric relaxation in the guinea pig, rat and ferret (Li & Rand, 1990;Boeckxstaens et al, 1992;Grider et al, 1992;Said, 1992;Grider & Jin, 1993;Grundy et al, 1993) and internal anal sphincter in the opossum (Chakder & Rattan, 1993). One possibility is that VIP acts partly through stimulation of NO formation, as has been suggested in the smooth muscle cells of the guinea pig stomach (Grider et al, 1992).…”

“…It has also been suggested that VIP and NO are co-transmitters of gastric relaxation in the guinea pig, rat and ferret (Li & Rand, 1990;Boeckxstaens et al, 1992;Grider et al, 1992;Said, 1992;Grider & Jin, 1993;Grundy et al, 1993) and internal anal sphincter in the opossum (Chakder & Rattan, 1993). One possibility is that VIP acts partly through stimulation of NO formation, as has been suggested in the smooth muscle cells of the guinea pig stomach (Grider et al, 1992). To examine this possibility we have localized NOS by immunocytochemistry to confirm that it is present in neurones and determined if there is any involvement of VIP in mediating vagally induced relaxation of the guinea pig stomach.…”

Comparison of Changes in the Interstitial Cells of Cajal and Neuronal Nitric Oxide Synthase-positive Neuronal Cells With Aging Between the Ascending and Descending Colon of F344 Rats

“…41,42 The NO level was significantly decreased in 2-year old rats as compared to 6-week old rats in the DC (P = 0.001), but not in the AC (P = 0.791) (Fig. 6A).…”

Impairment of nitrergic‐mediated relaxation of rat isolated duodenum by experimental diabetes

“…Based on the use of inhibitors of NO synthase (Rees et al, 1990;Moore et al, 1990) such as NG-monomethyl L-arginine (L-NMMA) or N0-nitroarginine (L-NOARG), NO has been proposed as a mediator of the non-adrenergic, non-cholinergic (NANC) relaxation of the intestinal smooth muscle, including that of rat or guinea-pig stomach and duodenum and the canine ileo-cecal juction and duodenum (Li & Rand, 1990;Bult et al, 1990;Toda et al, 1990;Desai et al, 1991;Irie et al, 1991). In addition, NO synthase has been located in the myenteric plexus and other neuronal structures of the rat gastro-intestinal tract (Bredt et al, 1990;Belai et al, 1992), although the contribution of the nitrergic neuronal enzyme to the overall NO synthase activity in the gastrointestinal tissues is not yet fully clear (Whittle et al, 1992;Grider et al, 1992; Sanders & Ward, 1992;Tepperman et al, 1993).…”