UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examines the integrative response of several duodenal functions to nitric oxide synthase inhibition. Effects of the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) were studied in anesthetized rats, using in situ duodenal perfusion. L-NAME increased bicarbonate secretion, permeability, and fluid secretion and induced motility. Injection of L-arginine abolished L-NAME-induced motility and lowered the secretion of bicarbonate and fluid. Pretreatment with the nicotinic receptor antagonist hexamethonium prevented the rise in bicarbonate secretion and motility in response to L-NAME but did not affect the increase in mucosal permeability. Atropine diminished the L-NAME-induced increases in permeability, motility, and fluid secretion. The adrenolytic drug guanethidine did not alter the responses to the inhibitor. These results suggest that nitric oxide inhibits duodenal motility and bicarbonate secretion by suppressing a stimulatory, nicotinic receptor-dependent, neural mechanism. The L-NAME-induced contractions involve both a cholinergic, atropine-sensitive pathway and nonadrenergic, noncholinergic neural transmission. Muscarinic receptors also mediate part of the L-NAME-induced increases in mucosal permeability and fluid secretion.
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PMID:Effects of nitric oxide inhibition on duodenal function in rat: involvement of neural mechanisms. 765 65

1. Neuromuscular transmission in the circular muscle of the canine proximal colon was examined, in the presence and absence of nitric oxide synthase inhibitors, by use of mechanical and intracellular microelectrode recording techniques. 2. Electrical field stimulation (EFS; 0.1-20 HZ) produced frequency-dependent contractions of circular muscle strips which reached a maximum at 15 Hz. These responses were enhanced by NG-monomethyl-L-arginine (L-NMMA; 300 microM) and reduced by atropine (1 microM). The effects of L-NMMA were reversed by L-arginine (3 mM). All responses to EFS were abolished by tetrodotoxin (1 microM). 3. In the presence of atropine, phentolamine and propranolol (all at 1 microM; 'non-adrenergic, non-cholingergic (NANC) conditions'), EFS evoked frequency-dependent inhibition of phasic contractions which reached a maximum at 5 Hz. At higher frequencies of EFS, inhibition diminished, and these responses were followed by post-stimulus excitation. 4. Under NANC conditions and in the presence of L-NG-nitroarginine methyl ester (L-NAME; 200 microM), EFS evoked contractions at frequencies of 5 Hz or greater. These contractions were reduced by co-incubation with L-arginine (2 mM) and abolished by tetrodotoxin (1 microM). 5. In the presence of atropine (1 microM), EFS (5-20 Hz) caused frequency-dependent inhibition of electrical slow waves. In the presence of L-NAME (100 microM) and atropine, the inhibitory response to EFS was abolished and an increase in slow wave duration was seen at stimulation frequencies greater than 5 Hz. The effects of EFS on slow wave duration were abolished by tetrodotoxin (1 microM). 6. Atropine-resistant contractions to EFS were enhanced by indomethacin (10 microM) and reduced or abolished by the non-selective NK1/NK2 tachykinin receptor antagonist D-Pro2, D-Trp7,9 SP, and by the selective NK2 receptor antagonist MEN 10,376 (10 microM).7. Exogenous tachykinins mimicked non-cholinergic excitatory electrical and mechanical responses. The rank order of potency for contraction was neurokinin A>neurokinin B>substance P, suggesting a predominance of the NK2 sub-type of tachykinin receptors on colonic smooth muscle cells. Low concentrations of neurokinin A also increased the amplitude and duration of electrical slow waves.8. These results suggest that: (i) in previous studies, non-cholinergic excitatory responses were masked by the simultaneous release of NO; (ii) non-cholinergic excitatory responses occur throughout the period of stimulation and are not manifest only as 'rebound' excitation; (iii) one or more tachykinins, possibly,acting via NK2 receptors, may mediate non-cholinergic excitatory responses.
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PMID:Inhibition of nitric oxide synthesis reveals non-cholinergic excitatory neurotransmission in the canine proximal colon. 768 1

1. Acetylcholine-induced contractions of the rat isolated anococcygeus muscle were blocked by atropine (0.1 microM), slightly enhanced by hexamethonium (0.1 mM) and tetrodotoxin (1 microM), but little affected by prazosin (0.1 microM). 2. In the presence of the alpha 2-adrenoceptor agonist, UK14304, which raised the tone of the muscle, acetylcholine had a biphasic effect consisting of an initial relaxation followed by a contraction. 3. Atropine (0.1 microM) enhanced the relaxant component and abolished the contractile component of the response, whereas tetrodotoxin, omega-conotoxin GVIA or hexamethonium abolished or greatly reduced the relaxant component. 4. The nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) increased acetylcholine-induced contractions in the absence of UK14304 and markedly reduced the relaxant component to acetylcholine in the presence of UK14304. The effects of L-NAME were annulled by L-arginine (300 microM). 5. The results suggest that acetylcholine acts concurrently on muscarinic receptors of the smooth muscle to cause contraction and nicotinic receptors of nitrergic nerves to cause relaxation. The observed response is the resultant of these two opposing effects and depends also on the prevailing tone.
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PMID:Modulation of acetylcholine-induced contractions of the rat anococcygeus muscle by activation of nitrergic nerves. 790 72

This study examined the role of nitric oxide (NO) in tonic inhibition of motor activity in isolated, perfused canine ileal segments. Brief addition of N omega-nitro-L-arginine methyl ester (L-NAME) to the perfusate caused, after a delay, a concentration-dependent persistent increase in tonic and phasic activity of circular muscle. This increased motor activity was prevented or reversed by addition of L- but not D-arginine to the perfusate. Removal of Ca2+ or addition of 10(-7) M omega-conotoxin (GVIA) to the perfusate markedly reduced this response. The motor activity induced by L-NAME was accompanied by loss of distal inhibition and enhanced excitation to low-frequency field stimulation. L-NAME infusion significantly reduced tonic vasoactive intestinal polypeptide (VIP) output, sodium nitroprusside increased VIP output, but L-arginine infusion did not restore VIP output. Atropine (10(-7) M) and/or hexamethonium (10(-4) M) reduced the motor response to L-NAME by 75%. Atropine reduced and hexamethonium nearly abolished VIP output. We conclude that there is tonic Ca(2+)-dependent NO output from perfused intestinal segments dependent on nerves with N-Ca channels, that NO acts to inhibit muscle directly and by inhibiting release of excitatory mediators, and that this output is the primary inhibitory determinant of contractile activity.
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PMID:Role of nitric oxide-related inhibition in intestinal function: relation to vasoactive intestinal polypeptide. 830 56

In chickens CCK-8s induces defecation and causes an inhibition of rectal electrical activity (EA) and an increase in cecal motility. In contrast, CCK-4 inhibits the motility of both rectum and ceca. The cecorectal responses to CCK-8s and CCK-4, given intravenously (i.v.), were studied in conscious chickens prepared with electrodes for electromyography; the influence of atropine, phentolamine plus propranolol, hexamethonium and L-NAME on such responses was determined. Atropine and phentolamine plus propranolol did not cause any change in the response to CCK-8s or CCK-4 in the cecorectal area. Hexamethonium only induced a significant decrease in the number of defecations (ND) induced by CCK-8s. L-NAME slightly modified the decrease in rectal EA due to CCK-8s. The effects of intracerebroventricular (i.c.v.) administration of CCK-8s and CCK-4 were also studied. CCK-8s and CCK-4, given i.c.v., caused, in conscious chickens, a slight decrease in cecal EA, in the 15 minutes following administration. This effect was similar to that seen after i.v. administration of CCK-4. In conclusion, our results suggest that the inhibitory action of CCK on chicken rectum is mediated, at least in part, through nitric oxide release. In addition, nicotinic receptors mediate the increase in the ND caused by CCK-8s. Ganglionic, muscarinic, adrenergic and nitrergic blockade were not able to modify the excitatory cecal response to CCK-8s, which may indicate that the receptor mediating this effect is located on the cecal smooth muscle. Finally, the inhibitory action of i.v. CCK-4 on chicken cecum seems to be centrally mediated, as suggested by the fact that i.c.v. administration of either CCK-8s or CCK-4 induce a similar effect.
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PMID:Central and NO mediated mechanisms are involved in the inhibitory effects of CCK on the chicken cecorectal area. 863 13

In the present study, mediators of muscle contraction-evoked cardiovascular responses were examined in anesthetized rats. Rhythmic contractions of the hindlimb triceps surae muscle were produced by stimulating the tibial nerve (motor threshold 22.7 +/- 2.3 microA; n = 10) by using a 1 s on-1 s off pattern. Mean arterial pressure (MAP) and heart rate (HR) responses were recorded before and after 1) muscarinic receptor blockade (atropine sulfate; 2.0 mg/kg i.v., n = 5); 2) nitric oxide synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME; 300 microM/kg i.v., n = 7); 3) beta-adrenoceptor blockade (propranolol; 2.0 mg/kg i.v., n = 10); and 4) bilateral adrenalectomy (n = 4). Rhythmic stimulation (10-s) significantly reduced MAP (P < 0.05) and elicited small decreases in HR that were abolished by neuromuscular blockade (n = 4). Atropine had no effect on MAP or HR responses to contraction. L-NAME increased baseline MAP (112.2 +/- 2.2 to 137.1 +/- 4.6 mmHg, P < 0.05) and attenuated contraction-evoked reductions of MAP (P < 0.05) without affecting HR. L-NAME-induced response deficits were mimicked in four separate rats by elevating MAP with phenylephrine (7-10 micrograms.kg-1.h-1 iv) to a level not different from that produced by L-NAME. Bilateral adrenalectomy and propranolol did not significantly affect HR responses but reduced contraction-evoked decreases in MAP from 14.3 +/- 2.9 to 7.7 +/- 2.2 mmHg and from 13.4 +/- 1.3 to 6.3 +/- 3.1 mmHg, respectively (P < 0.05). Baseline MAP was unchanged. We conclude that adrenal catecholamines, acting at beta-adrenoceptors, contribute significantly to the contraction-evoked depressor response in rats. No role for muscarinic receptors is evident in this response. Furthermore, attenuation of depressor responses to contraction after nitric oxide inhibition could result from an indirect effect of the pressor actions of L-NAME.
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PMID:Mediators of contraction-evoked skeletal muscle depressor response in anesthetized rats. 887 21

Several in vitro models of gastric relaxation have elucidated a role of nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) in non-adrenergic, non-cholinergic (NANC) vagally mediated gastric relaxation. However, these models do not necessarily mimic the events leading to gastric relaxation in the whole animal. We have recently described a vagally mediated gastric relaxation evoked by micro-injection of substance P (SP) into the nucleus raphe obscurus (NRO). The present study was performed to elucidate whether this CNS-stimulated in vivo gastric relaxation involved acetylcholine, NO and VIP. Atropine (1 mg kg-1 i.v.), reduces both the rapid nadir and sustained gastric relaxation evoked by SP in the NRO, and the residual responses are abolished by NG-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 10 mg kg-1 i.v.), an NO synthase inhibitor. Blockade of NO synthase alone is not sufficient to abolish the effect of SP into the NRO on intragastric pressure. A VIP antagonist, [p-chloro-D-Phe6, Leu17]VIP (32 micrograms i.v.) alone, or with the addition of L-NAME, does not affect the nadir of the gastric relaxation in response to SP microinjected into the NRO; however, both antagonists reduce the CNS-evoked sustained intragastric pressure relaxation. We conclude that, in CNS-evoked gastric relaxation, inhibition of cholinergic pathways is potentially important for both the rapid nadir and sustained gastric relaxation, and both NO and VIP contribute to sustained gastric relaxation.
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PMID:Contribution of acetylcholine, vasoactive intestinal polypeptide and nitric oxide to CNS-evoked vagal gastric relaxation in the rat. 895 35

The release of endogenous neurotransmitters plays an important role in the airway mucosal defense system. We studied the in vitro effect of methacholine, a beta-methyl ester of acetylcholine, on the ciliary beat frequency (CBF) of human adenoid explants and its mechanism of action. Tissue explants were cultured at 35 degrees C and covered with 1.0 mL of culture medium: minimum essential Eagle's medium (MEM) containing L-arginine (1.2 x 10(-3) mol/L). Methacholine was added to the cultured tissue at concentrations of 10(-10), 10(-8), and 10(-6) mol/L. The CBF was determined by phase contrast microscopy and microphotometry. Methacholine increased CBF in a dose-dependent manner with a maximum increase of 23.0% +/- 1.8% (p < .001). Atropine (10(-6) mol/L) significantly inhibited the ciliostimulatory effects of methacholine (p < .0007). The role of endogenous prostaglandins in methacholine-induced ciliostimulation was determined by treating specimens with a cyclooxygenase inhibitor (diclofenac sodium). Diclofenac (10(-6) mol/L) significantly inhibited the ciliostimulatory effects of methacholine (p < .0007). To determine if nitric oxide (NO) acts as an intermediary in ciliostimulation by methacholine, endogenous NO production was inhibited by treating specimens with an L-arginine analog, NG-nitro-L-arginine methyl ester (L-NAME), prior to addition of methacholine. L-NAME (10(-6) mol/L) inhibited the effects of methacholine in L-arginine-free MEM (p < .008), and this inhibition was reversed by L-arginine (10(-3) mol/L). To further examine the actions of NO in methacholine-induced ciliostimulation, a cyclic guanosine 3'5'-monophosphate (cGMP) kinase inhibitor (KT-5823) was used, prior to the addition of methacholine. KT-5823 (10(-6) mol/L) significantly inhibited the effects of methacholine (p < .0001). Ciliostimulation by methacholine in human upper airway mucosa involves both prostaglandin and NO second messengers and activation of a cGMP-dependent kinase.
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PMID:Signal transduction pathways in modulation of ciliary beat frequency by methacholine. 907 36

This study examined the physiological effects and potential mechanisms of action of methylecgonidine (MEG), the major pyrolysis product from smoking "crack cocaine," on cardiac function. Ferret right ventricular papillary muscles and human ventricular trabeculae were isolated and placed in a physiological solution at 30 degrees C containing 2.5 mM Ca2+ and stimulated at 0.33 Hz. MEG decreased peak tension and peak intracellular Ca2+ transients in a concentration-dependent manner (10 microM-1 mM). The negative inotropic effect (NIE) of MEG was reversible by atropine (1 microM). Atropine shifted the concentration-response curve of MEG rightward (pA2 = 9.17) similar to that of carbachol (pA2 = 8.70). With prior addition of histamine (1 microM) and Ca2+ (4.5 mM) in equiinotropic concentrations, MEG and carbachol decreased contractility to a greater extent in the histamine-stimulated muscles. To clarify whether the treatments altered responsiveness of the contractile elements to Ca2+, the effect of 2,3-butanedione monoxime (BDM), an agent that interferes with the interaction of actin and myosin, was tested after prior addition of histamine or increased Ca2+. No differential effect occurred. Moreover, the nitric oxide synthase inhibitor NG-nitro-L-arginine methylester (L-NAME; 0.1 mM), lessened the NIE of MEG compared with prior (pre-L-NAME) values. Furthermore, in human ventricular trabeculae (n = 7), MEG exhibited an NIE that was also reversible by atropine. We concluded that the NIE of MEG is caused by decreased calcium availability; the effect is not the result of a local anesthetic action but is mediated by stimulation of cholinergic receptors. This effect is potentiated by the nitric oxide pathway.
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PMID:Negative inotropic effect of methylecgonidine, a major product of cocaine base pyrolysis, on ferret and human myocardium. 930 Mar 20

Possible species differences and organ specificity in contractile or relaxation effects of an endogenous inotropic factor (EIF) isolated and purified from porcine heart left ventricle were examined in guinea pig and rat isolated atria, trabeculae and aortic smooth muscle rings. EIF demonstrated a dose-dependent increase in contractile force in guinea pig and rat atria and right ventricle trabeculae. The magnitude of the contractile effect was significantly lower in both the preparations of rat species as compared with guinea pig. In rat isolated aortic rings, EIF had no effect on the basal muscle tone. However, when rings were pre-contracted with phenylephrine EIF caused dose-dependent relaxation of the muscle. When aortic rings isolated from guinea pig were used, EIF induced a dose-dependent contraction which could be blocked by pre-treating the rings with either 2 microM phentolamine or 20 microM prazosin. When these same pre-treated rings were pre-contracted with histamine before the addition of EIF, a dose-dependent relaxation of guinea pig aortic smooth muscle rings was observed. Also depletion of catecholamines from the pre-synaptic nerve terminals innervating the aortic rings, using either 0.6 mM rauwolscine or reserpinizing (5 mg/Kg) the guinea pig 24 hours before sacrificing the animal, completely prevented EIF-induced contraction of the aortic rings. Instead EIF caused a dose dependent relaxation of the histamine pre-contracted aortic rings similar to that observed in rat aortic rings. The relaxation effect of EIF was demonstrated to be endothelium dependent and nitric oxide mediated in both species since EIF-induced relaxation could be inhibited by 2 microM L-NAME, a nitric oxide synthase inhibitor. Atropine (0.2 microM) or Indomethacin (10 microM) had no significant effect on EIF-induced relaxation of either guinea pig or rat aortic smooth muscle.
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PMID:Species differences in the effects of an endogenous inotropic factor (EIF) on the myocardium and aortic smooth muscle. 933 25

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