Mechanisms underlying the nitric oxide inhibitory effects in mouse ileal longitudinal muscle

2005 ◽  
Vol 83 (8-9) ◽  
pp. 805-810 ◽  
Author(s):  
Maria Grazia Zizzo ◽  
Flavia Mulè ◽  
Rosa Serio
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Mechanical Activity ◽  
Calcium Stores ◽  
Organ Bath ◽  
Inhibitory Effects ◽  
Longitudinal Smooth Muscle ◽  
Sarcoplasmatic Reticulum ◽  
Spontaneous Contractions ◽  
Mouse Ileum

We investigated the mechanisms involved in the nitric oxide (NO)-induced inhibitory effects on longitudinal smooth muscle of mouse ileum, using organ bath technique. Exogenously applied NO, delivered as sodium nitroprusside (SNP; 0.1–100 µmol/L) induced a concentration-dependent reduction of the ileal spontaneous contractions. 1H-[1,2,4]oxadiazolol[4,3,a]quinoxalin-1-one (ODQ; 1 µmol/L), a guanilyl cyclase inhibitor, reduced the SNP-induced effects. Tetraethylammonium chloride (20 mmol/L), a non-selective K+ channel blocker, and charybdotoxin (0.1 µmol/L), blocker of large conductance Ca2+-dependent K+ channels, significantly reduced SNP-induced inhibitory effects. In contrast, apamin (0.1 µmol/L), blocker of small conductance Ca2+-dependent K+ channels, was not able to affect the response to SNP. Ciclopiazonic acid (10 µmol/L) or thapsigargin (0.1 µmol/L), sarcoplasmatic reticulum Ca2+-ATPase inhibitors, decreased the SNP-inhibitory effects. Ryanodine (10 µmol/L), inhibitor of Ca2+ release from ryanodine-sensitive intracellular stores, significantly reduced the SNP inhibitory effects. The membrane permeable analogue of cGMP, 8-bromoguanosine 3′,5′-cyclic monophosphate (100 µmol/L), also reduced spontaneous mechanical activity, and its effect was antagonized by ryanodine. The present study suggests that NO causes inhibitory effects on longitudinal smooth muscle of mouse ileum through cGMP which in turn would activate the large conductance Ca2+-dependent K+ channels, via localized ryanodine-sensitive Ca2+ release.Key words: nitric oxide, mouse ileum, potassium channels, calcium stores.

scholarly journals Identification of serotonergic (5HT1A-type) receptors in broiler small intestine by application of serotonin and its agonists and antagonists

2011 ◽  
Vol 65 (1-2) ◽  
pp. 51-59 ◽  
Author(s):  
Indira Mujezinovic ◽  
Vitomir Cupic ◽  
Ahmed Smajlovic ◽  
Mehmed Muminovic
Keyword(s):  
Smooth Muscle ◽  
Small Intestine ◽  
Smooth Muscles ◽  
Muscle Layer ◽  
Force Transducer ◽  
Mechanical Activity ◽  
Organ Bath ◽  
Pathological Conditions ◽  
Isolated Organ Bath ◽  
Longitudinal Layer

Serotonin or 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter synthesised from L-tryptophan in serotonergic neurons and enterochromaffin cells of the gastrointestinal tract. This neurotransmitter is widely distributed in the animal and plant kingdom and regulates some central and peripheral functions through several types of specific serotonergic (5-HT) receptors. Since it is known that the effect of serotonin, especially in pathological conditions, is very important, we believe that determining the types of receptors for this substance would make it possible to use their agonist or antagonists, which would undoubtedly enhance the pharmacotherapy of functional disruption of the small intestine in broilers. Investigations were carried out on isolated smooth muscle strips of the circular and longitudinal layer of the broiler small intestine (strip dimension 3-4 mm x 2 cm). The muscle strips were placed in an isolated organ bath. The mechanical activity of the preparations was recorded via an isotonic force transducer coupled to a pen recorder. This was done following the addition of serotonin (nonselective 5-HT agonist), 8-OH-DPAT (selective 5-HT1A agonist) and spiroxatrin (selective 5-HT1A antagonist). The sensitivity of the tissues to acetylcholine was tested before starting the experiments. Using the obtained results, it can be concluded that 5HT1A type receptors are present in smooth muscles of the broiler small intestine, duodenum and ileum, especially in the longitudinal smooth muscle layer which reacted with contractions even to low serotonin concentration (10-6), but not in the jejunum.

PACAP and nitric oxide inhibit contractions in the proximal intestine of the atlantic cod, Gadus morhua

2000 ◽  
Vol 203 (3) ◽  
pp. 575-583 ◽  
Author(s):  
C. Olsson ◽  
S. Holmgren
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Intestinal Motility ◽  
Gadus Morhua ◽  
Atlantic Cod ◽  
Inhibitory Response ◽  
Nitric Oxide Donor ◽  
The Mean ◽  
Proximal Intestine ◽  
Spontaneous Contractions

The possible inhibitory roles of pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP) and nitric oxide in the control of intestinal motility were investigated in the Atlantic cod, Gadus morhua. Circular and longitudinal smooth muscle preparations developed spontaneous contractions that were inhibited by atropine (10(−)(5)mol l(−)(1)). PACAP 27 and PACAP 38 (10(−)(7)mol l(−)(1)) reduced the amplitude of the contractions but did not usually affect the resting tension. In the circular preparations, the mean active force developed (above resting level; +/− s.e.m.) was reduced from 0. 62+/−0.18 mN to 0.03+/−0.03 mN (N=10) by PACAP 27 and from 0.53+/−0. 20 mN to 0.31+/−0.13 mN (N=7) by PACAP 38, while neither cod nor mammalian VIP (10(−)(10)-10(−)(6)mol l(−)(1)) had any effect. In the longitudinal preparations, PACAP 27 reduced the force developed from 1.58+/−0.22 mN to 0.44+/−0.25 mN (N=8) and PACAP 38 reduced it from 1.61+/−0.47 mN to 0.75+/−0.28 mN (N=5). The nitric oxide donor sodium nitroprusside (NaNP) almost abolished the contractions in the circular preparations, reducing the mean force developed from 0. 47+/−0.05 mN to 0.02+/−0.06 mN (10(−)(6)mol l(−)(1); N=9) and 0+/−0. 07 mN (10(−)(5)mol l(−)(1); N=8). In the longitudinal preparations, NaNP reduced the force developed from 2.03+/−0.36 mN to 0.33+/−0.22 mN (10(−)(6)mol l(−)(1); N=8) and 0.19+/−0.30 mN (10(−)(5)mol l(−)(1); N=8). The L-arginine analogue N(G)-nitro-L-arginine methyl ester (L-NAME; 3×10(−)(4)mol l(−)(1)) enhanced the contractions in both circular and longitudinal preparations, increasing the mean force developed from 0.51+/−0.12 mN to 0.94+/−0.21 mN (N=8) and from 1.49+/−0.36 mN to 3.34+/−0.67 mN (N=7), respectively. However, preincubation with L-NAME before a second addition of PACAP 27 (10(−)(7)mol l(−)(1)) did not affect the response to PACAP, neither did preincubation with the guanylate cyclase inhibitor 6-anilinoquinoline-5,8-quinone (LY83583; 10(−)(5)mol l(−)(1)), while the inhibitory response to NaNP (3×10(−)(7)mol l(−)(1)) was abolished by LY83583. The PACAP analogue PACAP 6–27 (3×10(−)(7)mol l(−)(1)) had no effect on the response to either NaNP (3×10(−)(7)mol l(−)(1)) or PACAP 27 (10(−)(8)mol l(−)(1)) in the circular preparations. These findings indicate the presence of both a cholinergic and a nitrergic tonus in the smooth muscle preparations of the cod. Although PACAP and NaNP both inhibit contractions, there is no evidence of any interactions between the two substances. In addition, NaNP, but not PACAP, probably acts via stimulating the production of cyclic GMP. In conclusion, both PACAP and nitric oxide may act as inhibitory transmitters, using distinct signalling pathways, in the control of intestinal motility in the Atlantic cod.

scholarly journals Relaxin Affects Smooth Muscle Biophysical Properties and Mechanical Activity of the Female Mouse Colon

Endocrinology ◽  
2015 ◽  
Vol 156 (12) ◽  
pp. 4398-4410 ◽  
Author(s):  
Roberta Squecco ◽  
Rachele Garella ◽  
Eglantina Idrizaj ◽  
Silvia Nistri ◽  
Fabio Francini ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Protein Kinase ◽  
Guanylate Cyclase ◽  
Membrane Properties ◽  
Mechanical Activity ◽  
Biophysical Properties ◽  
Dependent Protein Kinase ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein

The hormone relaxin (RLX) has been reported to influence gastrointestinal motility in mice. However, at present, nothing is known about the effects of RLX on the biophysical properties of the gastrointestinal smooth muscle cells (SMCs). Other than extending previous knowledge of RLX on colonic motility, the purpose of this study was to investigate the ability of the hormone to induce changes in resting membrane potential (RMP) and on sarcolemmal ion channels of colonic SMCs of mice that are related to its mechanical activity. To this aim, we used a combined mechanical and electrophysiological approach. In the mechanical experiments, we observed that RLX caused a decay of the basal tone coupled to an increase of the spontaneous contractions, completely abolished by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one (ODQ). The electrophysiological results indicate for the first time that RLX directly affects the SMC biophysical properties inducing hyperpolarization of RMP and cycles of slow hyperpolarization/depolarization oscillations. The effects of RLX on RMP were abolished by ODQ as well as by a specific inhibitor of the cGMP-dependent protein kinase, KT5823. RLX reduced Ca2+ entry through the voltage-dependent L-type channels and modulated either voltage- or ATP-dependent K+ channels. These effects were abolished by ODQ, suggesting the involvement of the nitric oxide/guanylate cyclase pathway in the effects of RLX on RMP and ion channel modulation. These actions of RLX on membrane properties may contribute to the regulation of the proximal colon motility by the nitric oxide/cGMP/cGMP-dependent protein kinase pathway.

Simo Decoction Stimulates Contractions of Antral Longitudinal Smooth Muscle via Multitudinous Mechanisms

2012 ◽  
Vol 18 (2) ◽  
pp. 113-120 ◽  
Author(s):  
Chibing Dai ◽  
Wei Qian ◽  
Na Liu ◽  
Jing Gong ◽  
Wenmei Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Nicotinic Receptor ◽  
Adrenergic Receptor ◽  
Smooth Muscles ◽  
Maximal Effect ◽  
Krebs Solution ◽  
Contractile Responses ◽  
Longitudinal Smooth Muscle ◽  
M3 Receptor

The aim of the study was to investigate Simo decoction–induced contractions of antral smooth muscles of rats and its mechanisms. The contractile responses of longitudinal strips to consecutive concentrations of Simo decoction were characterized by atropine, gallamine, 4-diphenylacetoxy-N-methylpiperidine methiodide, and adrenaline, hexamethonium, L-arginine, and nifedipine and compared with Krebs solution (control) and acetylcholine-induced contractions. Simo decoction dose-dependently increased contractions of antral strips ( P = .000 vs control); its maximal effect was higher than acetylcholine (10−3 mol L−1; P < .05); Simo decoction–induced contractions were completely inhibited by atropine, 4-diphenylacetoxy-N-methylpiperidine methiodide, or 4-diphenylacetoxy-N-methylpiperidine methiodide + gallamine ( P = .000 for all) but were partly suppressed by gallamine, adrenaline, hexamethonium, L-arginine, and nifedipine ( P = .000 for all). Simo decoction promotes the contractions of antral strips mainly through activation of muscarinic M3 receptor, while partly through activation of M2 receptor, Ca2+ channel, nicotinic receptor, and inhibition of adrenergic receptor as well as release of nitric oxide.

Induction of nitric oxide synthase in rat gastric smooth muscle preparations

1997 ◽  
Vol 273 (5) ◽  
pp. G1101-G1107 ◽  
Author(s):  
Xi-Long Zheng ◽  
Keith A. Sharkey ◽  
Morley D. Hollenberg
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Nitric Oxide Synthase ◽  
Time Course ◽  
Inos Mrna ◽  
Organ Bath ◽  
Relaxant Response ◽  
Oxide Synthase ◽  
Inos Induction

The induction in vitro of inducible nitric oxide synthase (iNOS) in intact gastric circular (CM) and longitudinal (LM) smooth muscle preparations was evaluated 1) pharmacologically, by the appearance of 1 mM l-arginine (l-Arg)-induced relaxation in a precontracted tissue; 2) biochemically, according to the appearance of iNOS mRNA using a reverse transcriptase-polymerase chain reaction; and 3) immunohistochemically, using an iNOS-specific antibody. Functionally, iNOS induction affected the contractile properties of the CM but not the LM preparation. The time course of iNOS induction monitored pharmacologically paralleled exactly the appearance of iNOS mRNA. The relaxant response to l-Arg in iNOS-induced CM tissues was blocked by the iNOS inhibitor aminoguanidine and by the guanylyl cyclase inhibitor LY-83583. The addition of oxyhemoglobin to the organ bath also attenuated the relaxant response, but tetrodotoxin had no effect. The transcriptional inhibitor actinomycin D completely blocked iNOS induction as assessed by both pharmacological and biochemical criteria. In iNOS-induced preparations the iNOS immunoreactivity was not detected in the smooth muscle elements but was localized in a layer of macrophage-related cells that were in apposition to the CM smooth muscle elements. We conclude that the spontaneous induction of iNOS in rat gastric tissue can affect the pharmacomechanical reactivity of the CM elements and that this regulation of the CM contractility is due to the induction of iNOS in a set of macrophage-related cells that are closely apposed to the CM elements so that they selectively affect only the contractility of the CM preparation.

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