Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies were performed in the opossum to define the role of the L-arginine-nitric oxide (NO) pathway in lower esophageal sphincter (LES) relaxation to swallowing and vagal stimulation in viv and intramural nerve stimulation in vitro. In vivo, L-NAME, a water soluble NO synthase (NOS) inhibitor, caused antagonism of LES relaxation due to reflex-induced swallowing. L-NAME (20 mg/kg i.v.) reduced the amplitude of swallow induced relaxation from 88% to 28%. LES relaxation due to electrical stimulation of peripheral end of decentralized vagus nerve was also antagonized. The effects of L-NAME were reversed by L-arginine, but not by D-arginine. L-NAME treatment did not antagonize LES relaxation to intravenous administration of isoproterenol. In vitro, NO and sodium nitroprusside (SNP) caused a decrease in the sphincter tone. The relaxing effect caused by NO and SNP was not antagonized by tetrodotoxin or omega-conotoxin. Inhibitors of NO synthase, L-NMMA and L-NNA, caused slight increase in the spontaneous resting LES tone and concentration-dependent antagonism of electrical field stimulation (EFS) induced LES relaxation. L-NNA (10(-4)M) abolished EFS induced LES relaxation at low frequencies (less than 5 Hz) and antagonized the relaxation to a value 20% of the control at 20 Hz. The antagonistic action of L-NMMA and L-NNA was unaffected by D-arginine but was reversed by L-arginine. The inhibitory effect of NO, SNP, or two other putative inhibitory neurotransmitters (VIP and CGRP) on the LES was not antagonized by L-NNA. These studies show that inhibitors of NO synthase selectively antagonize LES relaxation to all three modes of intramural inhibitory nerve stimulation including physiological swallowing. These studies suggest that the L-arginine-nitric oxide pathway is involved in physiological relaxation of the LES.
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PMID:Role of nitric oxide in lower esophageal sphincter relaxation to swallowing. 137 90

The effects of trypsin and arginine analogues, alone or in combination, on half-maximal non-adrenergic, non-cholinergic (NANC) relaxation elicited by different pulse trains of electrical field stimulation were studied in the rat gastric fundus in order to investigate further the relative contribution of peptides and NO. Trypsin (1 microM) partially inhibited electrically-induced NANC relaxation especially when longer pulse trains were used. L-NOARG, L-NAME and L-NMMA, but not D-NOARG or D-NAME (3-300 microM) produced concentration-dependent inhibition of the electrically induced NANC relaxation. L-Arginine (L-Arg), but not D-Arginine (D-Arg) (3.8 microM-3.8 mM) produced a concentration-dependent reversal of the inhibitory effect of L-NOARG IC50 (38 microM). Neither L-NOARG (38 microM) nor L-Arg (380 microM) influence submaximal relaxation induced by VIP (3 nM), isopropylnoradrenaline (10 nM), ATP (10 microM) or sodium nitroprusside (300 nM). Moreover L-NOARG (100 microM) did not influence neurally-induced VIP release. L-NOARG inhibition of NANC relaxation was significant only when short pulse trains were used, while trypsin showed significant inhibition only of relaxation induced by longer pulse trains. These results suggest that the relaxation induced by the activation of the NANC inhibitory neurotransmission of the rat gastric fundus consists of at least two components, one trypsin-sensitive and the other trypsin-resistant, to which VIP and NO contribute, respectively.
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PMID:Evidence for dual components in the non-adrenergic non-cholinergic relaxation in the rat gastric fundus: role of endogenous nitric oxide and vasoactive intestinal polypeptide. 158 95

Mechanical and electrical activity in the antrum, pylorus, and duodenum was evaluated in the conscious dog, instrumented with seven strain gauges and five platinum electrodes. 17-Norleucine-vasoactive intestinal peptide (17-N-Leu-VIP) or 17-N-Leu-VIP plus NG-nitro-L-arginine methyl ester (L-NAME) was injected intra-arterially close to the pylorus to identify influences of nitric oxide (NO) on effects of VIP. VIP concentration was measured by radioimmunoassay in serum samples collected from the cubital and portal veins before and up to 2 h after VIP injection. VIP (0.004-0.006 mg.kg-1.10 min-1) abolished phasic contractions in the interdigestive state for 16.8 min and in the digestive state for 14.4 min, whereas whole serum VIP concentration rose above 42.4 +/- 13 pmol/l. Administration of L-NAME did not significantly influence the effects of VIP. Aftereffects of VIP, consisting of a reduced motility index, lasted 33 +/- 10.6 min in the interdigestive state and 44.5 +/- 42 min in the digestive state. This VIP aftereffect in the interdigestive state was shortened in time by the addition of L-NAME. The results overall suggest that NO release is a factor only in the aftereffects of VIP.
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PMID:Effect of 17-norleucine-VIP on gastroduodenal motility relative to serum VIP concentration and blockade of NOS. 748 11

1. We investigated the effect of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and the peptidase alpha-chymotrypsin on non-adrenergic, non-cholinergic (NANC neural) bronchoconstriction induced by electrical stimulation of the vagus nerves and by capsaicin in anaesthetized guinea-pigs in vivo using pulmonary insufflation pressure (PIP) as an index of bronchial tone. We also investigated the contribution of soluble guanylyl cyclase (SGC) to NANC neural relaxant mechanisms. 2. In the presence of atropine and propranolol, electrical stimulation of the vagus nerves induced a frequency-dependent increase in PIP above baseline of 67% at 2.5 Hz, of 128% at 5 Hz and of 230% at 10 Hz. L-NAME (1-50 mg kg-1, i.v.), at doses inducing increases in systemic blood pressure, dose-relatedly potentiated NANC bronchoconstriction. At 10 mg kg-1 i.v., L-NAME significantly (P < 0.05) potentiated NANC bronchoconstriction by a further 106% at 2.5 Hz and a further 147% at 5 Hz but did not potentiate the increase in PIP at 10 Hz. L-NAME did not induce bronchoconstriction in sham-stimulated control animals. D-NAME did not potentiate NANC bronchoconstriction. Raising systemic blood pressure with phenylephrine did not potentiate vagally-induced bronchoconstriction (2.5 Hz). 3. The NO precursor L-arginine, but not D-arginine, (100 mg kg-1, i.v.) significantly reversed the potentiation by L-NAME of NANC bronchoconstriction. L-Arginine alone significantly inhibited neurogenic bronchoconstriction at 10 Hz (by 74%); the inhibition of 25% at 2.5 Hz was not significant. 4. L-NAME did not significantly affect the increases in PIP induced by intravenous substance P. neurokinin A (NKA) or capsaicin. 5. The inhibitor of SGC, methylene blue (10 mg kg', i.v.) potentiated (by 110-140%) NANC neural bronchoconstriction induced by lower frequencies of nerve stimulation and reversed the reduction in PIP induced by the SGC activator, sodium nitroprusside (SNP, 1.05 mg kg- 1, i.v.). SNP significantly (P <0.05) reduced by 65% the bronchoconstriction induced by nerve stimulation at 10 Hz. Methylene blue did not effect baseline PIP in sham-stimulated controls. The airway effects of methylene blue and SNP were not associated with their cardiovascular effects. 6. a-Chymotrypsin (2 units kg-', i.v.) significantly potentiated vagally-induced bronchoconstriction by a further 63% at 2.5 Hz, by a further 95.6% at 5 Hz but did not potentiate the increase in PIP at 10 Hz. alpha-Chymotrypsin also potentiated (by 116%) capsaicin-induced bronchoconstriction. Vasoactive intestinal peptide (VIP, 10 ig kg-' i.v. infused over min) significantly reduced by 70% the increase in PIP induced by NKA (0.1 .Lmol kg-' i.v., infused over 30 s). 7. The combination of a-chymotrypsin (2 units kg-', i.v.) and L-NAME (5 mg kg-', i.v.) significantly potentiated NANC bronchoconstriction by a further 304% at 2.5 Hz, an increase in PIP which was greater than that induced by either a-chymotrypsin or L-NAME alone (P <0.05). 8. We conclude that endogenous NO and a bronchodilator peptide, possibly VIP, released in association with nerve stimulation, as well as activation of soluble guanylyl cyclase, regulate the magnitude of NANC neurogenic bronchoconstriction in guinea-pigs in vivo.
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PMID:Regulation of NANC neural bronchoconstriction in vivo in the guinea-pig: involvement of nitric oxide, vasoactive intestinal peptide and soluble guanylyl cyclase. 767 32

1. Electrical field stimulation (EFS) of intrinsic nerves in the rat proximal duodenum induces a frequency-dependent non-adrenergic-non-cholinergic (NANC) relaxation response. 2. The inhibitors of L-arginine-NO synthase L-NG-nitro arginine methyl-ester (L-NAME) and L-NOARG (L-NG-nitro arginine) reduced the NANC relaxations elicited by EFS in a dose- and time-dependent manner; L-NOARG was two times more potent than L-NAME (IC50 = 14.3 vs 25.2 microM) and these effects were partially reverted by the addition of 300-1000 microM L-arginine but not of 300-1000 microMD-arginine. Relaxation caused by vasoactive intestinal peptide (VIP; 0.1 microM) or ATP (20 microM) was not blocked by L-NAME or L-NOARG. 3. The magnitude of the blockade caused by L-NAME and L-NOARG was dependent on the frequency of stimulation. At low frequencies (below 1 Hz) both L-NAME and L-NOARG abolished the relaxations, while at 2 to 8 Hz only partial inhibition was observed (maximal inhibition: 44.6% +/- 5.2 and 63.4% +/- 3.4, respectively) 4. The basal tonus of the duodenum was increased by 10-300 microM L-NAME and 10-300 microM L-NOARG and this effect was blocked by 1 mM L-arginine. 5. Nitric oxide generated from acidified NaNO2 caused a dose-dependent (EC50 = 2.75 microM) relaxation of the duodenum which was not affected by 100 microM L-NAME, 100 microM L-NOARG or 1 microM tetrodotoxin (TTX). 6. NADPH-diaphorase positive neurons and fibers identified by histochemistry were present in the myenteric plexus and along both circular and longitudinal muscle fibers indicating that nitric oxide could be synthetized by these neural structures.
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PMID:Evidence for the participation of the L-arginine-nitric oxide pathway in neurally induced relaxation of the isolated rat duodenum. 813 34

Formation of NO, enzymatically catalyzed by NO synthases in both endothelial cells and autonomic nerves, seems to explain some noncholinergic nonadrenergic tissue reactions. We studied the possible role of NO in vagally induced pancreatic exocrine secretion using isolated perfused porcine pancreas (n = 11) with intact vagus nerve (VN) supply. Electrical stimulation of the VN (8 Hz, 10 mA) and infusions of vasoactive intestinal polypeptide (VIP, 2 x 10(-9) M) were carried out before and after addition to the perfusate of the NO synthase inhibitors N omega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) or NG-nitro-L-arginine (L-NNA, 10(-5) M) with and without further addition of L-arginine (10(-3) M). We also studied the effects of L-arginine alone and of sodium nitroprusside (10(-4) M). In all experiments VN and VIP caused a profuse exocrine secretion (43 +/- 7 and 44 +/- 11 times basal secretion). The inhibitors increased vascular resistance approximately twofold but had no effect on the vascular relaxation caused by VIP and VN. The exocrine fluid response to VN was reduced to 19 +/- 5 and 4.7 +/- 1.8% (L-NAME and L-NNA), and response to VIP was reduced to 54 +/- 12 and 35 +/- 13%. Protein and bicarbonate outputs largely paralleled flow rate. Addition of L-arginine (no effects alone) to L-NAME restored the responses to VN (to 100 +/- 21% of controls) and increased VIP responses (to 65 +/- 11%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of nitric oxide in neurally induced pancreatic exocrine secretion in pigs. 814 Dec 93

1. Relaxations of strips of rat gastric fundus were elicited with nicotine (100 mumol/L), nitric oxide (NO; 30 mumol/L), sodium nitroprusside (SNP; 100 nmol/L) and vasoactive intestinal polypeptide (VIP; 1 nmol/L). 2. Methylene blue (30 mumol/L), an inhibitor of soluble guanylate cyclase, reduced relaxations elicited by NO and nicotine, but not those elicited by VIP. 3. Chymotrypsin (1 U/mL) abolished VIP-induced relaxations and reduced nicotine-induced relaxations, but had no effect on SNP-induced relaxations. 4. NG-nitro-L-arginine methyl ester (L-NAME; 100 mumol/L), an inhibitor of NO synthase, reduced relaxations elicited by nicotine, but not those elicited by SNP or VIP. 5. When nicotine-induced relaxations had been reduced by either L-NAME or chymotrypsin, the addition of the other agent produced a greater reduction. However, the relaxations were not abolished. 6. Nicotine-induced relaxations were abolished by tetrodotoxin (1 mumol/L) or hexamethonium (100 mumol/L), indicating that they were due to activation of neuronal nicotinic receptors. Their reduction by methylene blue and L-NAME indicates that an NO-like mediator was involved. Their reduction by chymotrypsin indicates that a VIP-like peptide was involved. However, since they were not abolished by a combination of L-NAME and chymotrypsin, it appears that at least one more as yet unidentified mediator may be involved.
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PMID:Mediators of nicotine-induced relaxations of the rat gastric fundus. 833 69

The roles of VIP and NO in vagally mediated relaxations of the gastric corpus were investigated in the anaesthetized ferret. Intracorpus pressure was recorded manometrically during electrical stimulation of the cervical vagus nerve in three groups of animals: one control group (n = 6), one group treated with an inhibitor of NO synthesis (NG-nitro-L-arginine methyl ester (L-NAME), 1.6 mg/kg); and a third group which had been immunized, prior to the experiment, with a VIP-thyroglobulin conjugate (25 nmol equivalent) in Freund's complete adjuvant. In control animals, following treatment with atropine (100 micrograms/kg), vagal stimulation resulted in a frequency dependent fall in intracorpus pressure with the maximum response at 5 Hz of 2.2 +/- 0.3 cm H2O. Two components of the response could be observed: an initial rapid fall over the first 10 s of stimulation followed by a slower decline over the remainder of the stimulation period. In animals treated with L-NAME (n = 6) the initial rapid response was significantly reduced at all frequencies of stimulation (P < 0.05 - P < 0.005, Mann-Whitney U-test) leaving only the slower second component. In immunized animals (n = 6) the initial rapid response to vagal stimulation was not different from control but the slower second component was significantly reduced at 1 Hz (P < 0.005). We conclude that the response to vagal stimulation appears to consist of two components which can be differentiated using L-NAME and autoimmunization to VIP.
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PMID:Role of nitric oxide and vasoactive intestinal polypeptide in vagally mediated relaxation of the gastric corpus in the anaesthetized ferret. 836 53

Smooth muscle cells distributed in the visceral organs are under the control of the autonomic nervous system, and contraction or relaxation of the muscle cells plays an important physiological role in the control of blood pressure, motility of the digestive, respiratory and urinary tracts and secretion. Recent physiological, pharmacological and histochemical investigations indicate that neurotransmitters other than acetylcholine or noradrenaline are involved in peripheral autonomic neuro-effector transmission, and these neurotransmitters are generally termed non-adrenergic, non-cholinergic (NANC) neurotransmitters. The neurotransmitters responsible for excitatory and inhibitory NANC neurotransmission (e-NANC and i-NANC respectively) have not been conclusively identified, but ATP, nitric oxide (NO) and peptides such as VIP and substance P are candidates for these roles. In this review, we discuss the possible role of ATP and NO as e- or i-NANC neurotransmitter in the digestive, respiratory and urinary tracts. Much of the work on NANC innervation in the digestive tract has been carried out on the circular muscle layers of the ileum. This receives inhibitory NANC innervation with ATP responsible for fast relaxation and VIP, and possibly NO, for the slow response. Early and late excitatory junction potentials can be recorded in the presence of atropine. The second is due to substance P since it is blocked in the presence of spantide and by desensitization of the tissue with high doses of substance P. The transmitter responsible for the early NANC contraction has not been identified. Electrical field stimulation (EFS) applied to the tracheal smooth muscle during contraction induced by 5-HT in the presence of atropine and guanethidine elicited monophasic NANC relaxation. By contrast, NANC relaxation elicited in the smaller airways was biphasic, comprising an initial fast component followed by a second slow one. L-NAME selectively abolished the first component without affecting the second. VIP-antagonists or alpha-chymotrypsin considerably attenuated the amplitude of the L-NAME insensitive relaxation. These results indicate that at least two neurotransmitters, possibly NO or NO-containing compounds and VIP, are involved in i-NANC neurotransmission in the airway. In the urinary bladder a large, transient atropine resistant contraction occurs in response to pelvic nerve stimulation. This is blocked by alpha, beta methylene ATP suggesting that it is due to ATP. There is no evidence of inhibitory innervation. In the urethra contraction is completely blocked by atropine and guanethidine; a rapid NANC relaxation is abolished by drugs that block NO synthesis. Nerves containing peptides supply both urethra and bladder and may also be involved. These results suggest that all visceral smooth muscles may receive inhibitory NANC innervation involving NO. ATP produces contraction of the urinary bladder but relaxation of the digestive tract. The role of peptides is not yet clear but there is evidence that substance P may be an excitatory transmitter and VIP an inhibitory transmitter in many organs.
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PMID:[The control of smooth muscle tissues by nonadrenergic noncholinergic (NANC) nerve fibres in the autonomic nervous system]. 856 58

1. The effect of 8-week streptozotocin-induced diabetes has been examined on relaxations to non-adrenergic, non-cholinergic (NANC) nerve stimulation in longitudinal strips of rat gastric fundus. 2. In the presence of noradrenergic and cholinergic blockade and raised tissue tone, electrical field stimulation (0.5-4 Hz, 30 s trains) induced frequency-dependent relaxations that were significantly smaller in gastric fundus strips from diabetic rats than in strips from control rats. 3. NG-nitro-L-arginine methyl ester (NAME, 100 microM) significantly reduced NANC relaxations in muscle strips from both control and diabetic rats, but the reduction was greater in muscle strips from diabetic rats than in those from control rats at frequencies of 2 and 4 Hz. alpha-Chymotrypsin (1 u ml-1) slightly reduced relaxations to nerve stimulation in muscle strips from both control and diabetic rats. 4. The duration of NANC nerve relaxations (1-4 Hz, 30 s trains) was smaller in muscle strips from diabetic rats than in those from control rats. The duration of NANC relaxations was reduced by alpha-chymotrypsin (1 u ml-1) in muscle strips from control rats but not in muscle strips from diabetic rats. 5. Relaxations to both nitric oxide (NO; 1-30 microM) and vasoactive intestinal polypeptide (VIP; 0.1-30 microM) were concentration-dependent and did not differ between muscle strips from control and diabetic rats. 6. The results suggest that streptozotocin-induced diabetes impairs relaxations to NANC nerve stimulation in the rat gastric fundus, which are largely mediated by NO and to a lesser extent by VIP. The impairment appears to occur at the prejunctional level, as smooth muscle reactivity to NO and VIP is not altered.
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PMID:Effect of diabetes on relaxations to non-adrenergic, non-cholinergic nerve stimulation in longitudinal muscle of the rat gastric fundus. 856 18


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