Possible Involvement of ATP-Sensitive K+ Channels in the Inhibition of Rat Central Adrenergic Neurotransmission under Hypoxia

Abstract

ABSTRACT-The role of cyclic GMP (cGMP) in nonadrenergic, noncholinergic (NANC) relaxation of the longitudinal muscle of rat proximal and distal colon was examined. Electrical field stimulation (EFS) of preparations of longitudinal muscle from the proximal region significantly increased the cGMP content. Nitro-L-arginine inhibited this increase, and L-arginine reversed the inhibitory effect of nitro-L-arginine. Exogenously added nitric oxide (NO) and atrial natriuretic peptide (ANP) also increased the cGMP content of preparations of the proximal colon and induced muscle relaxation. From these and our previous findings suggesting an essential role of NO in NANC inhibition in the proximal colon, we conclude that the mechanism of NANC inhibition in the proximal region of rat colon involves NO and a cGMP generating system. In contrast, although exogenously added NO and ANP increased the cGMP content in the distal colon to the same extent as in the proximal colon, they did not induce any muscle relaxation. Vasoactive intestinal peptide (VIP), the most likely candidate as a NANC neurotransmitter in rat distal colon, did not increase the cGMP content in this region. Furthermore, no participation of NO in the NANC inhibitory response was observed in the distal region, but EFS increased the cGMP content significantly. Thus we con clude that relaxation of longitudinal smooth muscle in the distal portion of rat colon is not associated with a change in the cGMP content.Keywords: Cyclic GMP, Nitric oxide (NO), Vasoactive intestinal peptide (VIP), Nonadrenergic, noncholinergic (NANC) inhibition, Colonic motility Several lines of evidence suggest that nitric oxide (NO) is a mediator of the nonadrenergic, noncholinergic (NANC) inhibitory response in various parts of the gas trointestinal tract, including the caecum (1) and stomach (2, 3) of guinea pigs; the gastric fundus (4, 5), duodenum (6) and proximal colon (7) of rats; and human ileum (8).The release of NO was suggested to occur during nerve stimulation of the canine ileocolonic junction (9) and rat gastric fundus (10). The high immunoreactivity of NO synthase in the myenteric plexus throughout the gut (11, 12) also supports the idea that NO is involved in the NANC inhibitory response. At present, the exact mechanism of the action of NO is unknown. Some reports suggest that NO and other nitrovasodilators induce relaxation of vascular smooth muscle cells by increasing the cyclic GMP (cGMP) con tent (13 16). There is also recent evidence that cGMP for mation is involved in the non-vascular smooth muscle relaxation elicited by NO or NO-producing compounds in preparations of taenia coli (17), corpus cavernosum (18, 19), tracheal (20) and ileal (21) smooth muscle. In these preparations, the relaxant effects of NO or NO-producing compounds were closely associated with an elevation of the intracellular cGMP level. NO was reported to activate soluble guanylate cyclase and increase the cGMP level in various tissue preparations (22). These observations strongly support the idea that ...

Nitric oxide‐mediated relaxation without concomitant changes in cyclic GMP content of rat proximal colon

“…However, the same concentration of the inhibitor did not affect the DMPP-and EFS-induced relaxations (Table 1) not only the stimulatory effect of DMPP on the cyclic GMP content and decreased it below the resting level ( Figure 3). As we have already shown, EFS also increased the cyclic GMP content of the preparations (Suthamnatpong et al, 1993b;Figure 4).…”

“…EFS of the preparations significantly increased the guanosine 3':5'-cyclic monophosphate (cyclic GMP) content and L-NOARG inhibited while L-arginine reversed this inhibition. Exogenous nitric oxide increased the cyclic GMP content of the preparations (Suthamnatpong et al, 1993b). We also showed a relaxant effect of cyclic GMP in 'skinned smooth muscle' preparations obtained from the longitudinal muscle layer of rat proximal colon (Maehara et al, 1994).…”

VIP‐ and PACAP‐mediated nonadrenergic, noncholinergic inhibition in longitudinal muscle of rat distal colon: involvement of activation of charybdotoxin‐ and apamin‐sensitive K+ channels

“…Our previous studies suggested that NANC relaxation in longitudinal muscle of the rat distal colon was not associated with the nitric oxide-cyclic GMP generating system (Suthamnatpong et al, 1993a), although EFS or exogenous nitric oxide significantly increased cyclic GMP content of the colonic longitudinal muscle with myenteric plexus preparations (Suthamnatpong et al, 1993b;Maehara et al, 1994). Our present study strongly suggests that NANC-induced relaxation in the longitudinal muscle of the rat distal colon is mediated by VIP and PACAP which activate charybdotoxinand apamin-sensitive K+ channels, respectively.…”

Mechanism of a Nitric Oxide Donor NOR 1-Induced Relaxation in Longitudinal Muscle of Rat Proximal Colon

“…NO is known to increase the intracellular cyclic GMP content through an activation of soluble guanylate cyclase in vascular smooth muscles (7). It was also shown that NO or EFS which induces NO-mediated relaxation, increased the cyclic GMP content in the smooth muscle cells in the rat ileum (8) and proximal colon (9). These results suggest that NO induces the relaxation of smooth muscle by increasing the cyclic GMP content.…”