Nitrergic and purinergic regulation of the rat pylorus

Abstract

The role of nitric oxide (NO) and ATP in the regulation of nonadrenergic, noncholinergic (NANC) inhibitory transmission in the pylorus remains unclear. In the presence of atropine and guanethidine, electric field stimulation induced NANC relaxations in a frequency-dependent manner (1-20 Hz) in the rat pylorus. NANC relaxations were significantly inhibited by N(G)-nitro-L-arginine methyl ester (L-NAME; 10(-4) M). P(2X) purinoceptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 3 x 10(-5) M) and P(2Y) purinoceptor antagonist reactive blue 2 (2 x 10(-5) M) had no effect on NANC relaxations. However, the combined administration of L-NAME and PPADS, but not reactive blue 2, evoked greater inhibitory effects on NANC relaxation than that evoked by L-NAME alone. alpha-Chymotrypsin and vasoactive intestinal polypeptide antagonist did not affect NANC relaxations. ATP (10(-5)-10(-3) M) and P(2X) purinoceptor agonist alpha, beta-methyleneadenosine 5'-triphosphate (10(-7)-10(-5) M), but not P(2Y) purinoceptor agonist 2-methylthioadenosine 5'-triphosphate (10(-7)-10(-5) M), induced muscle relaxations in a dose-dependent manner, and relaxations were significantly reduced by PPADS and unaffected by TTX. These studies suggest that NO and ATP act in concert to mediate NANC relaxation of the rat pylorus. ATP-induced relaxation appears to be mediated by P(2X) purinoceptors located on smooth muscle cells.

Pharmacologic Characterization of Intrinsic Mechanisms Controlling Tone and Relaxation of Porcine Lower Esophageal Sphincter

“…We found that the apamin-sensitive component of EFS relaxation is strongly inhibited by MRS 2179, showing that a purine mediates this component by acting on P2Y 1 receptors; it is slightly but consistently inhibited by NF 279, also suggesting the involvement of P2X 1,2,3 receptors; and it is slightly inhibited by the peptidase chymotrypsin, suggesting that PACAP (an apamin-sensitive peptidergic neurotransmitters) also has a minor role in EFS-induced relaxation. Similar results on the involvement of P2Y1 and also P2X 1,2,3 receptors on inhibitory neurotransmission were found in the mouse jejunum (De Man et al, 2003), and ATP-induced relaxation of rat pylorus has been attributed to muscular P2X purinoceptors (Ishiguchi et al, 2000). Heme oxygenase inhibitors did not modify Fig.…”

“…Smooth muscle cells along the gastrointestinal tract can simultaneously express G-protein-coupled P2Y receptors mediating the relaxatory effects of purines and ion-gated P2X receptors mediating either contractions (Giaroni et al, 2002) or relaxations (Storr et al, 2000). Activation of P2X receptors could initially induce an increase in intracellular Ca 2ϩ leading a contraction and a relaxation as a result of secondary activation of apamin-sensitive Ca 2ϩ -dependent K ϩ -channels (Ishiguchi et al, 2000). MRS 2179 is a specific antagonist for P2Y 1 purinoreceptor subtype (De Man et al, 2003) that in our study strongly antagonized the ATP relaxation.…”

“…In addition, the similarity of the responses in experiments with ODQ (where nitric oxide is synthesized and released and could induce the release of any other neurotransmitter) and L-NAME (where nitric oxide is not synthesized) argues against release of VIP or any other neurotransmitter by nitric oxide (Grider et al, 1992) and also against nitric oxide inhibition of the release of ATP (Ishiguchi et al, 2000). Our results suggest mechanisms of simultaneous release and independent actions (cotransmission) for the nitrergic, purinergic, and peptidergic inhibitory neurotransmitters released during EFS.…”

Gastric distension‐induced pyloric relaxation: central nervous system regulation and effects of acute hyperglycaemia in the rat

“…Our recent study showed that NANC relaxations were significantly inhibited by L-NAME, suggesting the mediation by neuronal release of NO (Ishiguchi et al 2000b). …”

Gastrointestinal Function Regulation by Nitrergic Efferent Nerves

“…Soediono and Burnstock (1994) have concluded that ATP seems to act through P 2Y -purinoceptors in the rat pyloric sphincter. Studies on the rat pylorus by Ishiguchi et al (2000) have also shown that NO and ATP act in concert to mediate NANC relaxation. However, these authors suggested that P 2X purinoceptors are involved in the ATP-induced relaxation.…”