Contribution of NK2 tachykinin receptors to propulsion in the rabbit distal colon

2000 ◽  
Vol 278 (1) ◽  
pp. G137-G147 ◽  
Author(s):  
L. Onori ◽  
A. Aggio ◽  
G. Taddei ◽  
M. Tonini
Keyword(s):  
Nitric Oxide ◽  
Circular Muscle ◽  
Distal Colon ◽  
Inhibitory Effect ◽  
Facilitatory Effect ◽  
Nitric Oxide Synthase Inhibitor ◽  
Excitatory Transmission ◽  
The Difference ◽  
High Concentrations ◽  
Synthase Inhibitor

The role of the tachykinin neurokinin (NK)2 receptors on rabbit distal colon propulsion was investigated by using two selective NK2-receptor antagonists, MEN-10627 and SR-48968. Experiments on colonic circular muscle strips showed that contractile responses to [β-Ala8]NKA-(4—10) (1 nM–1 μM), a selective NK2-receptor agonist, were competitively antagonized by MEN-10627 (1–100 nM), whereas SR-48968 (0.1–10 nM) caused an insurmountable antagonism, thus confirming the difference in the mode of action of the two compounds. Colonic propulsion was elicited by distending a mobile rubber balloon with 0.3 ml (submaximal stimulus) or 1.0 ml (maximal stimulus) of water. The velocity of anal displacement of the balloon (mm/s) was considered the main propulsion parameter. At low concentrations (1.0–100 nM and 0.1–10 nM, respectively), MEN-10627 and SR-48968 facilitated the velocity of propulsion, whereas at high concentrations (100 nM and 1 μM, respectively) they decelerated propulsion. The excitatory and inhibitory effects of both antagonists were observed only with submaximal stimulus. We focused on the hypothesis that the facilitatory effect on propulsion may result from blockade of neuronal NK2 receptors and the inhibitory effect from suppression of the excitatory transmission mediated by NK2 receptors on smooth muscle cells. In the presence of N G-nitro-l-arginine (300 μM), a nitric oxide synthase inhibitor, MEN-10627, at a concentration (10 nM) that was found to accelerate propulsion in control experiments inhibited the velocity of propulsion. In the presence of threshold (1–10 nM) or full (1 μM) concentration of atropine, which inhibited to a great extent the velocity of propulsion, the inhibitory effect of MEN-10627 (1 μM) was markedly increased. In conclusion, in the rabbit distal colon NK2 receptors may decelerate propulsion by activating a nitric oxide-dependent neuronal mechanism and may accelerate it by a postjunctional synergistic interaction with cholinergic muscarinic receptors.

Peristalsis regulation by tachykinin NK1 receptors in the rabbit isolated distal colon

2003 ◽  
Vol 285 (2) ◽  
pp. G325-G331 ◽  
Author(s):  
Luciano Onori ◽  
Annalisa Aggio ◽  
Gennaro Taddei ◽  
Maria F. Loreto ◽  
Rachele Ciccocioppo ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Circular Muscle ◽  
Distal Colon ◽  
Inhibitory Effect ◽  
Model System ◽  
Suitable Model ◽  
Nitric Oxide Synthase Inhibitor ◽  
Inhibitory Pathways ◽  
Synthase Inhibitor ◽  
Oxide Synthase

In the gastrointestinal tract, tachykinin NK1 receptors are widely distributed in a number of neuronal and nonneuronal cells involved in the control of gut motor activity. In particular, in the rabbit isolated distal colon, which is a suitable model system to investigate the contribution of tachykinins as noncholinergic excitatory transmitters, the influence of NK1 receptors in the regulation of peristalsis is not known. The selective NK1-receptor antagonists SR-140333 (0.3 and 1 nM) and MEN-10930 (0.3–10 nM) significantly enhanced the velocity of rabbit colonic propulsion to submaximal stimulation. The prokinetic effect of SR-140333 was prevented by Nω-nitro-l-arginine (l-NNA), a nitric oxide synthase inhibitor, indicating that NK1 receptors located on nitrergic innervation exert a functional inhibitory restraint on the circular muscle and probably on descending excitatory and inhibitory pathways during propulsion. Conversely, the selective NK1-receptor agonist septide (3–10 nM) significantly inhibited colonic propulsion. In the presence of l-NNA, the inhibitory effect of septide was reverted into a prokinetic effect, which is probably mediated by the activation of postjunctional excitatory NK1 receptors.

Isoflurane Anesthesia Attenuates Endothelium-dependent Pulmonary Vasorelaxation by Inhibiting the Synergistic Interaction between Nitric Oxide and Prostacyclin 

1997 ◽  
Vol 86 (4) ◽  
pp. 936-944 ◽  
Author(s):  
Linda M. Gambone ◽  
Paul A. Murray ◽  
Nicholas A. Flavahan
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Arteries ◽  
Inhibitory Effect ◽  
Isometric Tension ◽  
Synergistic Interaction ◽  
Nitric Oxide Synthase Inhibitor ◽  
Channel Dependent ◽  
The Individual ◽  
Synthase Inhibitor ◽  
Endothelium Dependent Relaxation

Background Endothelium-derived nitric oxide causes vasodilation in part by increasing the dilator activity of other endothelium-derived mediators, including prostacyclin and a K+ATP channel-dependent hyperpolarizing factor. Although previous studies have proposed that isoflurane (ISO) depresses endothelium-dependent vasorelaxation by inhibiting endothelium-derived nitric oxide activity, the effects of ISO on the interactions among endothelium-derived dilators have not been characterized. The aim of this study was to determine the mechanisms underlying the inhibitory effect of ISO on endothelium-dependent relaxation in canine pulmonary arteries. Specifically, the goal was to assess the effects of ISO on the individual actions and on the synergistic interactions of these endothelium-derived mediators. Methods Canine pulmonary arterial rings were suspended for isometric tension recording. The effects of 1 minimum alveolar concentration ISO (0.4 mM) on vasorelaxation responses to bradykinin, A23187, acetylcholine, cromakalim, and SIN-1 were assessed in phenylephrine-precontracted rings with and without pretreatment with a nitric oxide synthase inhibitor (N omega-nitro-L-arginine methyl ester; L-NAME), a cyclooxygenase inhibitor (indomethacin), or a K+ATP channel inhibitor (glybenclamide). Results Isofluane attenuated pulmonary vasorelaxation induced by bradykinin, A23187, and cromakalim but had no effect on relaxation induced by acetylcholine or SIN-1. Neither the nitric oxide-mediated nor the prostacyclin-mediated components of relaxation induced by bradykinin and A23187 were altered by ISO. However, ISO abolished the K+ATP-mediated component of relaxation and the K+ATP-dependent synergistic interaction between nitric oxide and prostacyclin. Conclusions These results suggest that ISO selectively attenuates endothelium-dependent relaxation in canine pulmonary arteries. It exerts its inhibitory effect by interfering with a synergistic interaction between nitric oxide and prostacyclin, possibly via an effect on K+ATP channels.

scholarly journals Electromagnetic Fields Inhibit Endothelin-1 Production Stimulated by Thrombin in Endothelial Cells

2005 ◽  
Vol 33 (5) ◽  
pp. 545-554 ◽  
Author(s):  
S Morimoto ◽  
T Takahashi ◽  
K Shimizu ◽  
T Kanda ◽  
K Okaishi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Nitric Oxide Synthase Inhibitor ◽  
Endothelin 1 ◽  
Synthase Inhibitor

Electromagnetic field (EMF) radiation has been found to induce arteriolar dilatation, but the mechanism of action remains largely unknown. This study investigated the effect of EMF radiation on the production of endothelin-1 (ET-1), a potent vasoconstrictor, by cultured endothelial cells. EMF radiation reduced ET-1 basal levels in human umbilical vein and microvascular endothelial cells, but failed to reduce ET-1 basal levels in bovine and human aortic endothelial cells. EMF radiation significantly inhibited thrombin-stimulated ET-1 production in all four endothelial cell types in a dose-dependent manner. EMF radiation significantly inhibited thrombin-induced endothelin-1 mRNA expression in all four cell types. The inhibitory effect of EMF radiation on ET-1 production was abolished by the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (10−3 mol/l). These results demonstrate that EMF radiation modulates ET-1 production in cultured vascular endothelial cells and the inhibitory effect of EMF radiation is, at least partly, mediated through a nitric oxide-related pathway.

scholarly journals Inhibitory effect of valves on endothelium-dependent relaxations to calcium ionophore in canine saphenous vein

2001 ◽  
Vol 280 (2) ◽  
pp. H892-H898 ◽  
Author(s):  
Daihiko Eguchi ◽  
Zvonimir S. Katusic
Keyword(s):  
Nitric Oxide ◽  
Soluble Guanylate Cyclase ◽  
Isometric Force ◽  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Nitric Oxide Synthase Inhibitor ◽  
A 23187 ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Endothelium Dependent Relaxation

The present study was designed to evaluate endothelium-dependent relaxation to the calcium ionophore A-23187 in isolated canine saphenous veins. Isometric force recordings and cGMP measurements using isolated veins with and without valves were performed. During contractions to U-46619 (3 × 10−7 M), endothelium-dependent relaxations to A-23187 (10−9–10−6 M) were significantly reduced in rings with valves compared with rings without valves. Endothelial removal abolished A-23187-induced relaxation. Relaxations to forskolin (FK; 10−8–10−5 M) and diethylaminodiazen-1-ium-1,2-dionate; DEA-NONOate, 10−9–10−5 M) were identical in rings with and without valves. In rings without valves, a nitric oxide synthase inhibitor, N G-nitro-l-arginine methyl ester (l-NAME; 3 × 10−4 M), and a cyclooxygenase inhibitor, indomethacin (10−5 M), partially reduced A-23187-induced relaxation. However, in rings with valves,l-NAME had no effect, whereas indomethacin abolished the relaxation to A-23187. A selective soluble guanylate cyclase inhibitor, 1 H-[1,2,4]-oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 3×10−6 M), had no effect on the relaxation to A-23187 in either group. In contrast, ODQ abolished the A-23187-induced increase in cGMP levels, suggesting that relaxation to nitric oxide released by A-23187 is independent of increases in cGMP. These results demonstrate that endothelium-dependent relaxation to A-23187 is reduced in regions of veins with valves compared with relaxation in the nonvalvular venous wall. Lower production of nitric oxide in endothelial cells of valvular segments appears to be a mechanism responsible for reduced reactivity to A-23187.

Regulation of colonic propulsion by enteric excitatory and inhibitory neurotransmitters

1996 ◽  
Vol 271 (3) ◽  
pp. G433-G437 ◽  
Author(s):  
A. E. Foxx-Orenstein ◽  
J. R. Grider
Keyword(s):  
Nitric Oxide ◽  
Circular Muscle ◽  
Neurokinin A ◽  
Maximal Inhibition ◽  
Nitric Oxide Synthase Inhibitor ◽  
Inhibitory Neurotransmitters ◽  
Peristaltic Reflex ◽  
In Series ◽  
Synthase Inhibitor ◽  
Oxide Synthase

The contribution of excitatory and inhibitory motor neurotransmitters to colonic propulsion was examined in isolated segments of guinea pig colon. Synthetic fecal pellets were inserted at the proximal end of the segment, and the velocity of pellet propulsion across a fixed distance was measured in the presence and absence of selective neurotransmitter antagonists. The control velocity (0.97 +/- 0.02 mm/s) was inhibited in a concentration-dependent fashion by atropine and the neurokinin (NK)-2a antagonist MEN-10,376 [half-maximal inhibitory concentration (IC50), 1 microM; maximal inhibition, 98 +/- 1%]. The NK-1 antagonist GR-82,334 (10 microM) also inhibited velocity by 65 +/- 9%, consistent with involvement of acetylcholine, neurokinin A (NK-2 agonist), and substance P (NK-1 agonist) in the contractile components of the peristaltic reflex. Velocity was also inhibited in a concentration-dependent fashion by the nitric oxide synthase inhibitor NG-nitro-L-arginine (L-NNA; IC50, 1 microM; maximal inhibition, 96 +/- 2%) and by the vasoactive intestinal peptide (VIP) antagonist VIP-(10-28) (IC50, 30 nM; maximal inhibition, 64 +/- 6%), consistent with involvement of both nitric oxide and VIP in descending relaxation of circular muscle and contraction of longitudinal muscle. A combination of threshold concentrations of L-NNA and the NK-2a antagonist was synergistic (53 +/- 7% inhibition). The potentiation implied that the ascending and descending phases were functionally coupled in series. We conclude that blockade of neurotransmitters that mediate either phase of the peristaltic reflex inhibits colonic propulsive activity. Serial coupling of the phases leads to synergism between inhibitors, a condition of potential therapeutic importance.

Glomerular and tubular interactions between renal adrenergic activity and nitric oxide

1995 ◽  
Vol 268 (6) ◽  
pp. F1004-F1008 ◽  
Author(s):  
F. B. Gabbai ◽  
S. C. Thomson ◽  
O. Peterson ◽  
L. Wead ◽  
K. Malvey ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Glomerular Filtration ◽  
Renal Nerves ◽  
Ang Ii ◽  
Nitric Oxide Synthase Inhibitor ◽  
Adrenergic Activity ◽  
Single Nephron ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Endothelium-dependent nitric oxide (EDNO) exerts control over the processes of glomerular filtration and tubular reabsorption. The importance of the renal nerves to the tonic influence of EDNO in the glomerular microcirculation and proximal tubule was tested by renal micropuncture in euvolemic adult male Munich-Wistar rats. The physical determinants of glomerular filtration and proximal reabsorption were assessed before and during administration of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), in control animals and in animals 5–9 days after either ipsilateral surgical renal denervation (DNX) or after either sham surgery (SHX). L-NMMA caused single-nephron glomerular filtration rate to decline in control and SHX animals but not in DNX rats. L-NMMA caused a reduction in proximal reabsorption in control and SHX rats, which was prevented by prior DNX. DNX did not alter urinary guanosine 3',5'-cyclic monophosphate excretion, and, although DNX upregulates glomerular angiotensin II (ANG II) receptors, prior DNX did not alter intrarenal ANG II content as evaluated by radioimmunoassay. Some component of renal adrenergic activity is required for the full expression of the glomerular and tubular effects of blockade of nitric oxide synthase.

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