The role of nitric oxide and l-type calcium channel blocker in the contractility of rabbit ileum in vitro

Abstract

Nitric oxide (NO) and calcium channel blockers are two agents that can affect gastrointestinal motility. The goal of this work was to study the rabbit intestinal smooth muscle contraction response to (1) sodium nitroprusside (SNP), the NO donor, and its potential mechanism of action, and (2) nifedipine, the L-type Ca(2+) channel blocker; to clarify the degree of participation by extra- and intracellular Ca(2+) in smooth muscle contraction. We used standard isometric tension and intracellular micro-electrode recordings. To record the activity of the longitudinal smooth muscle of the ileum, segments of 1.5 cm length of the ileum were suspended vertically in organ baths of Krebs solution. The mechanical activity of the isolated ileal longitudinal muscle was recorded. Different substances were added, and the changes produced on spontaneous contraction were recorded. We found that SNP produced significant decrease, while nitric oxide synthase inhibitor produced significant increase in the amplitude of spontaneous contractions. Both apamin, the Ca(2+)-dependent K(+) channel blocker, and methylene blue, the inhibitor of soluble guanylate cyclase, alone, partially decreased relaxation induced by SNP. Addition of both methylene blue and apamine together abolished the inhibitory effect produced by SNP on spontaneous contractions. Nifedipine produced significant decrease in the amplitude of spontaneous contractions. In conclusion, in longitudinal muscle of rabbit ileum, calcium channels blocker are potent inhibitors of spontaneous activity. However, both extracellular and intracellular Ca(2+) participates in the spontaneous contractions. NO also has inhibitory effect on spontaneous activity, and this effect is mediated by cGMP generation system and Ca(2+)-dependent K(+) channels.

Myorelaxant effect of aqueous root bark extract of Carissa edulis (Forssk.) Vahl. is mediated through activation of nitric oxide synthase

“…Indeed, Nitric oxide-sensitive guanylyl cyclase has been shown to be dispensable for nitregic signaling and gut motility in intestinal (Groneberg et al, 2011). In this study, L-Nitroarginine methyl ester and methylene blue increased the basal tone of spontaneous jejunal contraction; these findings are similar to those (Ragy and Elbassuoni, 2012) in which the same doses of the above blockers also caused an increase in the basal tone of rabbit jejunal contraction. The β adrenergic receptors mediate their inhibitory effect on rabbit jejunum through cAMP and PKA (Cavalcante-Silva et al, 2016) .…”

Receptors and mechanisms mediating the biphasic response evoked by bradykinin in rat colonic smooth muscle

“…), an inhibitor of the main cellular target enzyme of NO, i.e., the soluble guanylate cyclase, 20 had any effect on the response evoked by bradykinin (Table 2). In rat duodenum, the bradykinin-induced relaxation has been shown to be caused by the activation of Ca 2+ -dependent K + channels.…”

“…However, the response to the kinin was not altered by indomethacin. Moreover, a release of nitric oxide, which is well known to induce intestinal relaxation, is obviously not involved, as neither a blockade of NO synthases with L-NAME (10 À5 mol L À1 ) nor methylene blue (10 À5 mol L À1 ), an inhibitor of the main cellular target enzyme of NO, i.e., the soluble guanylate cyclase, 20 had any effect on the response evoked by bradykinin ( Table 2). In rat duodenum, the bradykinin-induced relaxation has been shown to be caused by the activation of Ca 2+dependent K + channels.…”

17β-Estradiol Inhibites Nitric Oxide-cGMP-Dependent Pathway but may Activate Independent Pathway in Small Intestinum of Ovariectomized Rat

“…Firstly, NO 2 reduces levels of Ca ++ within a cell and increases the permeability of K + channels. Thus, it hyperpolarizes the plasma membrane [15,16] . Secondly, cGMP blocks miyozin/ aktin interaction by activating cGMP dependent protein kinaz (PKG) which leads to the dephosphorization of light miyozin chains and which is reported to play a key role in NO/cGMP signals [15] .…”