Investigation of the interaction between nitric oxide and vasoactive intestinal polypeptide in the guinea‐pig gastric fundus

Abstract

1 The interaction between nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) was investigated in isolated circular smooth muscle cells and strips of the guinea-pig gastric fundus. 2 VIP induced a concentration-dependent inhibition of carbachol-induced contraction in smooth muscle cells with a maximum at 10 76 M. The relaxation by 10 76 M VIP was inhibited for 79.1+5.8% (mean+s.e.mean) by the NO-synthase (NOS) inhibitor L-N G -nitroarginine (L-NOARG; 10 74 M) in a L-arginine reversible way. Also the inducible NOS (iNOS) selective inhibitor N-(3-(acetaminomethyl)-benzyl)acetamide (1400 W; 10 76 M) inhibited the VIP-induced relaxation, but its inhibitory e ect was not reversed by L-arginine. 3 When cells were incubated with the guanylyl cyclase inhibitor 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ, 10 76 M), the protein kinase A-inhibitor (R)-p-cyclic adenosine-3',5'-monophosphothioate ((R)-p-cAMPS, 10 76 M) and the glucocorticoid dexamethasone (10 75 M), the relaxant e ect of VIP was decreased by respectively 80.9+7.6, 77.0+11.6 and 87.1+4.5%. 4 In circular smooth muscle strips of the guinea-pig gastric fundus, the VIP (10 79 ± 10 77 M)-induced relaxations were not signi®cantly in¯uenced by 10 74 M L-NOARG, 10 76 M 1400 W, 10 76 M ODQ and 10 75 M dexamethasone. 5 These results suggest that iNOS, possibly induced by the procedure to prepare the smooth muscle cells, is involved in the relaxant e ect of VIP in isolated smooth muscle cells but not in smooth muscle strips of the guinea-pig gastric fundus. This study illustrates the importance of the experimental method when studying the in¯uence of NOS inhibitors on the relaxation induced by VIP in gastrointestinal smooth muscle preparations.

Roles of PACAP and PHI as inhibitory neurotransmitters in the circular muscle of mouse antrum

“…These results indicate that NO mediates the rapid phasic relaxation in the mouse antrum. A role of NO in phasic relaxation was observed in the porcine antrum [34] and in fundus strips of various animal species [7,10,12]. Therefore, NO may be a mediator for the rapid phasic relaxation induced by EFS in these regions of the stomach.…”

“…Participation of nitric oxide (NO) in the transient relaxation was reported in the gastric fundus strips of guinea pig [10], rat [29], mouse [12], pig [9] and human [39]. However, the mediator responsible for sustained relaxation remains controversial.…”

Acute exercise inhibits gastric emptying of liquids in rats: influence of the NO-cGMP pathway

“…On the day of the experiment, the animals were randomly treated with vehicle (0.9% NaCl, 0.1 mL/100g, ip ) or one of the following agents: the muscarinic receptor antagonist (atropine, 1.0 mg/kg, ip ) (17), the NO non-selective inhibitor Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10 mg/kg, ip ) (18), the cGMP selective inhibitor 1H-(1,2,4)oxadiazole[4,3-a]quinoxalin-1-one (ODQ; 5.0 mg/kg, ip ) (19), the i-NOS non-selective inhibitor (aminoguanidine 10 mg/kg, ip ) (20), the CRF receptor antagonist (astressin 100 µg/kg, ip ) (21), or the VIP receptor antagonist Lys 1 , Pro 2,5 , Arg 3,4 , Tyr 6 (100 µg/kg, ip ) (19). Thirty minutes after pretreatment, the rats were subjected to the formerly specified sedentary or acute exercise protocols.…”

Leukotriene-induced contraction is mediated by cysteinyl leukotriene receptor CysLT1 in guinea pig fundus but by CysLT1 and CysLT2 in antrum

“…The strips were connected to isometric transducers (FT.03; Grass Technologies, West Warwick, RI, USA), which were connected to an amplifier (Gould Instrument Systems, Valley View, Ohio, USA) and a computer recording system (BIOPAC systems, Goleta, CA, USA). The basal tension of the fundic and antral muscle strips was adjusted to 1.0 g (Chang et al, 2008;Huang, 2009;Dick et al, 2000;von Schrenck et al, 1989). Experiments were started after a 45 min equilibration period.…”

“…Measurements of contraction of isolated fundic and antral strips were performed according to the procedure published previously with minor modifications (Chang et al, 2008;Huang, 2009;James et al, 2005;Dick et al, 2000;von Schrenck et al, 1989). In brief, the isolated fundic and antral strips were attached to organ baths using surgical silk sutures and incubated at 37°C in the standard incubation solution continuously gassed with 95% O 2 • 5% CO 2 .…”