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

1. To investigate the distribution profile of functional inhibitory non-adrenergic non-cholinergic (i-NANC) nerves and the contribution of NO to the NANC relaxation in the cat, we studied the effects of N omega-nitro-L-arginine methyl ester (L-NAME) on NANC relaxation elicited by electrical field stimulation (EFS) in the trachea, bronchus and bronchiole. 2. EFS applied to the tracheal smooth muscle during contraction induced by 5-HT (10(-5) M) in the presence of atropine (10(-6) M) and guanethidine (10(-6) M) elicited a monophasic NANC relaxation. By contrast, NANC relaxation elicited in the peripheral airway was biphasic, comprising an initial fast followed by a second slow component and L-NAME (10(-5) M) selectively abolished the first component without affecting the second one. In the trachea, L-NAME (10(-5) M) completely suppressed the monophasic NANC relaxation when single or short repetitive stimuli (< 5) with 1 ms pulse duration were applied. However, at higher repetitive stimuli (> 10) with 1 or 4 ms pulse duration, suppression of NANC relaxation was incomplete. 3. In the small bronchi obtained from L-NAME-pretreated cats, EFS applied during contraction induced by 5-HT (10(-5) M) elicited only the slow component of NANC relaxation which is sensitive to tetrodotoxin. 4. In the peripheral airway, a newly synthesized VIP antagonist (10(-6) M) or alpha-chymotrypsin (1 U ml-1) considerably attenuated the amplitude of L-NAME-insensitive relaxation. 5. Single or repetitive EFS consistently evoked excitatory junction potentials (EJPs) in the central and peripheral airways. When tissues were exposed to atropine (10(-6) M) and guanethidine (10(-6) M), single or repetitive EFS did not alter the resting membrane potential. 6. These results indicate that at least two neurotransmitters, possibly NO or NO-containing compounds and VIP, are involved in i-NANC neurotransmission and the distribution profile of the two components differs in the central and peripheral airway of the cat.
 ...
PMID:Regional difference in the distribution of L-NAME-sensitive and -insensitive NANC relaxations in cat airway. 857 60

1. Inhibitory junction potentials (IJPs) and relaxations evoked in response to field stimulation (supramaximal voltage, 0.1 ms, single stimulus and 5 stimuli at 5-40 Hz) of non-adrenergic non-cholinergic (NANC) nerves with atropine and phentolamine (each 1 microM) were measured in the guinea-pig internal anal sphincter (gpIAS). The mean resting membrane potential was -44.2 +/- 0.2 mV (n = 1119 cells from 260 preparations). 2. NANC nerve stimulation evoked frequency-dependent IJPs (19.7 +/- 1.1 mV, n = 165, 33 tissues to a single stimulus) and relaxations. IJPs consisted of two tetrodotoxin (1 microM)-sensitive components: one was abolished by apamin (0.3 microM) and the P2-purinoceptor antagonist suramin (100 microM); the other, smaller in amplitude, was sensitive to inhibitors of nitric oxide synthase (NOS, e.g. L-NAME, 100 microM) and the nitric oxide (NO) scavenger oxyhaemoglobin (HbO, 10 microM). 3. ATP (1 mM), vasoactive intestinal polypeptide (VIP, 0.01-0.25 microM) and pituitary adenylate cyclase-activating peptide (PACAP(1-27), 0.84 microM) each hyperpolarized and relaxed the gpIAS; only ATP responses resembled the evoked IJPs in time course. 4. The guanylyl cyclase inhibitor LY83583 (10 microM) abolished apamin-insensitive IJPs and relaxations. The cGMP phosphodiesterase inhibitor M&B 22948 (30 microM) and 8-Br-cGMP (100 microM) each hyperpolarized the gpIAS. 5. Two components comprise the IJP and relaxation evoked in response to NANC nerve stimulation in the gpIAS. One, sensitive to apamin, resembles the response to ATP and is modulated by purinoceptor antagonists; the other, apamin and suramin insensitive, is inhibited by NO antagonists.
 ...
PMID:Neuronal mediators of inhibitory junction potentials and relaxation in the guinea-pig internal anal sphincter. 878 13

1. RR may act as a preferential capsaicin antagonist in the pig nasal mucosa in vivo. However, the present data reveal a narrow concentration range for the selective actions of RR. Moreover, RR has systemic cardiovascular side effects despite local i.a. infusion in the IMA. 2. Acoustic rhinometry is a useful method for investigations of changes in nasal cavity volume in the pig in vivo. 3. The NK1-receptor antagonist RP-67,580 lacks NK1-receptor blocking properties in the pig in vivo. In contrast, CP-96,345 and SR 140.333 significantly blocked SP-mediated vascular effects in the pig nasal mucosa and superficial skin, indicating species dependent NK1-receptor selectivity. Capsaicin-induced vasodilatation in the IMA was not attenuated after administration of CP-96,345 and SR 140.333 whereas the superficial blood flow in the nasal mucosa and skin was slightly reduced. The CGRP-receptor antagonist hCGRP 8-37 markedly reduced the capsaicin-evoked vascular effects in the pig nasal mucosa and superficial skin. 4. Vanilloid receptors, as revealed by 3H-RTX binding, are present in the pig nasal mucosa although with different characteristics compared to vanilloid receptors in the pig dorsal horn. Capsaicin, RTX and LA evoked vasodilatation in the pig nasal mucosa in a similar fashion, indicating activation of sensory nerves. The LA (proton)-evoked vasodilatation was significantly attenuated after local i.a. infusion of hCGRP 8-37, closely resembling the results obtained from the capsaicin challenge before and after CGRP-receptor blockade. Capsazepine did not reduce the capsaicin-and LA-evoked vasodilation in the pig nasal mucosa. This agrees well with the observation that capsazepine did not inhibit RTX binding to vanilloid receptors in pig nasal mucosal membranes. 5. Capsaicin desensitisation of the human nasal mucosa attenuated the subjective pain response as well as the reduction of the cross-sectional area in the nasal cavity evoked by LA and hypertonic saline. This finding gives further support to the hypothesis that protons may act as endogenous ligands to the vanilloid receptor also in man. 6. Systemic administration of the NOS inhibitor L-NNA significantly reduced basal nasal V Con and increased C Vol in the pig. The effects evoked by L-NNA were similar in magnitude to those of phenylephrine and UK 14304, although of much longer duration. Administration of L-NNA did not reduce the vasodilator responses to SP and ACh, suggesting that these substances may mediate their vascular effects via one or several other mechanisms beside the NO/cGMP pathway. Moreover, capsaicin-, VIP-, and nitroprusside-evoked vasodilatation was not reduced after NOS inhibition. 7. Heavy physical exercise and alpha-adrenoceptor agonists reduce nasal cavity NO levels acutely in man. This may be due to a reduced supply of substrates for NO synthesis in the paranasal sinus epithelium, the primary NO production site in the upper airways. However, prolonged use of the alpha 2-adrenoceptor agonist oxymetazoline for 10 days, did not reduce basal nasal cavity NO levels. Nasal cavity NO levels and C Vol were not altered after topical administration of the NOS inhibitor L-NAME. Nor did we see any change in C Vol after local challenge with NO gas in the nasal cavity. The present results indicate that the human nasal mucosa is largely insensitive to NO gas in contrast to the bronchial mucosa and lung. 9. In conclusion, the present results suggest that vanilloid receptors are present on sensory nerves in the pig nasal mucosa and that LA (protons) may act as an endogenous ligand to this receptor. Sensory neuropeptides, especially CGRP, may be of importance for nasal congestion upon sensory nerve activation. Hence, selective, non-peptide CGRP-receptor antagonists may be of potential use in nasal disorders characterised by nasal congestion. NO is of importance for basal nasal vascular regulation. However, whether NOS inhibitors have potential as useful nasal de
 ...
PMID:Sensory neuropeptides and nitric oxide in nasal vascular regulation. 880 Mar 74

Small arteries (internal diameter 376 +/- 69 microns) from the proximal intestine region of the rainbow trout were mounted in a myograph apparatus where changes in isometric tension could be recorded. VIP (vasoactive intestinal polypeptide) caused a concentration-dependent relaxation (10(-9)-3 x 10(-7) M) of vessels precontracted with the alpha-adrenoceptor agonist phenylephrine (10(-5) M). The nitric oxide synthase inhibitor L-NAME (10(-4) M) did not affect the VIP-relaxation, neither did the lipoxygenase inhibitor esculetin (10(-5) M). However, the cyclooxygenase inhibitor indomethacin (10(-6) M) shifted the concentration-response curve significantly to the right. The VIP-relaxation was still present after mechanical removal of the endothelium. Sodium nitroprusside (10(-9)-10(-6) M) caused a concentration-dependent relaxation of the precontracted vessel, indicating the presence of soluble guanylate cyclase in the vascular smooth muscle cells. VIP-immunoreactivity was found in varicose nerve fibers in these vessels, but nitric oxide synthase-immunoreactivity could not be demonstrated. These results suggest that in rainbow trout, as in mammals, VIP is an endogenous vasodilating neuropeptide. No endothelium-dependent mechanism seems to be involved, neither is production of nitric oxide. Instead the relaxation is mediated, at least in part, via prostaglandin synthesis.
 ...
PMID:Vip-induced relaxation of small arteries of the rainbow trout, Oncorhynchus mykiss, involves prostaglandin synthesis but not nitric oxide. 908 41

In anaesthetized guinea pigs, adenosine enhances the histamine-induced bronchospasm by means of a mechanism partly involving non-adrenergic-non-cholinergic (NANC) nerves, not related to capsaicin-sensitive neurons (Breschi et al., 1994). In the present paper, we excluded any interference by adenosine with the mediators known to be present in the airway inhibitory NANC system, VIP (vasoactive intestinal polypeptide) and NO (nitric oxide). The use of alpha-chymotrypsin or L-N(G)-nitro-arginine methyl ester (L-NAME) failed to modify the potentiation under study. The effects of adenosine were further investigated by studying whether an increased release of excitatory mediators from non-neural cells, in particular 5-HT (5-hydroxytryptamine, serotonin) and arachidonic products, was involved. In this connection, methysergide did not significantly affect the modulatory action of adenosine, revealing that the release of 5-HT was also not involved. Inhibition was obtained with hydrocortisone and with nordihydroguaiaretic acid, but not with indomethacin or with the mastocyte membrane stabilizer, sodium cromoglycate. This evidence suggests that lipooxygenase products, not derived from mastocytes, probably participate in the potentiating effect of adenosine.
 ...
PMID:Histaminic bronchospasm potentiated by adenosine: investigation of the mechanisms. 927 81

To assess the role of ORL1 (opioid receptor-like 1) receptor in the bowel movement, we investigated the effect of nociceptin on colonic contraction and transit in rats. Nociceptin (0.1-100 nM) concentration-dependently caused an immediate tonic contraction followed by rhythmic waves of contractions in the isolated colon. The response to nociceptin (10 nM) was not affected by the classical opioid receptor antagonists, naloxone, naltrindole and nor-binaltorphimine. Suppression of effect of inhibitory neurotransmitters using pituitary adenylate cyclase activating polypeptide(6-38) (PACAP-(6-38); 3 microM), vasoactive intestinal polypeptide(10-28) (VIP-(10-28); 3 microM) and N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 microM) did not influence the nociceptin-induced contractions. In anesthetized rats, intravenous administration of nociceptin (1 microg/kg) or morphine (1 mg/kg) caused phasic contractions in the proximal colon. Pretreatment with naloxone (300 microg/kg, i.v.) abolished the contractions induced by morphine, but not by nociceptin. The rate of large intestinal transit was dose-dependently accelerated by nociceptin (0.03-3 microg/kg, s.c.), but was retarded by morphine (1.7-5 mg/kg, s.c.). These results indicate that stimulation of ORL1 receptor accelerates the colonic contraction and transit independently from opioid receptors.
 ...
PMID:The effect of nociceptin, an endogenous ligand for the ORL1 receptor, on rat colonic contraction and transit. 972 56

Blood flow in salivary glands is regulated mainly by sympathetic and parasympathetic nerve activity. This study was carried out to determine the relative contributions of cholinergic, adrenergic and peptidergic neurotransmitters to the control of submandibular blood flow in the rat using laser-Doppler flowmetry. Parasympathetic impulses caused a rapid atropine-sensitive vasodilation followed by a maintained increase in blood flow, a portion of which remained in the presence of both atropine and L-NAME. In contrast, continuous sympathetic stimulation caused an intense vasoconstriction that was followed by a prolonged after-vasodilation. The same number of impulses delivered in bursts resulted in a cyclic vasoconstriction followed by a rapid vasodilation. Alpha-adrenoceptor blockade largely abolished the vasoconstriction, and the duration and magnitude of the after-vasodilation were reduced. Inhibition of nitric oxide (NO) synthase by L-NAME reduced the vasodilation. The addition of a beta-adrenoceptor antagonist eliminated the sympathetic vasodilator response, but in the presence of complete alpha- and beta-adrenoceptor blockade and L-NAME a small vasoconstriction remained. We conclude that the vasoconstrictor effects of sympathetic stimulation of the rat submandibular gland are due to alpha-adrenergic receptor activation and probably also NPY, and the vasodilator effects are due to NO and beta-adrenergic activity. Parasympathetic vasodilation was due to NO-independent mechanisms mediated by acetylcholine and substance P, and NO-dependent mechanisms mediated by VIP.
 ...
PMID:Neural regulation of blood flow in the rat submandibular gland. 982 25

1. Electrical field stimulations (EFS) of the opossum and canine lower oesophageal sphincters (OLOS and CLOS respectively) and opossum oesophageal body circular muscle (OOBCM) induce non-adrenergic, non-cholinergic (NANC) relaxations of any active tension and NO-mediated hyperpolarization. VIP relaxes the OLOS and CLOS and any tone in OOBCM without major electrophysiological effects. These relaxations are not blocked by NOS inhibitors. Using isolated smooth muscle cells, we tested whether VIP acted through myogenic NO production. 2. Outward currents were similar in OOBCM and OLOS and NO increased them regardless of pipette Ca2+(i), from 50-8000 nM. L-NAME or L-NOARG did not block outward currents in OLOS at 200 nM pipette Ca2+. 3. Outward currents in CLOS cells decreased at 200 nM pipette Ca2+ or less but NO donors still increased them. VIP had no effect on outward currents in cells from OOBCM, OLOS or CLOS under conditions of pipette Ca2+ at which NO donors increased outward K+ currents. 4. We conclude, VIP does not mimic electrophysiological effects of NO donors on isolated cells of OOBCM, OLOS or CLOS. VIP relaxes the OLOS and CLOS and inhibits contraction of OOBCM by a mechanism unrelated to release of myogenic NO or an increase in outward current. 5. Also, the different dependence of outward currents of OOBCM and OLOS on pipette Ca2+ from those of CLOS suggests that different K+ channels are involved and that myogenic NO production contributes to K+ channel activity in CLOS but not in OLOS or OOBCM.
 ...
PMID:Activation of outward K+ currents: effect of VIP in oesophagus. 1038 58

1 Guanethidine is commonly used as a drug to investigate adrenergic neurotransmission and, in combination with atropine, to realize non-adrenergic non-cholinergic (NANC) conditions. Previous studies suggested a nicotinic acetylcholine receptor blocking effect of guanethidine. Therefore, we investigated the effect of increasing concentrations of guanethidine (0.1-100 microM) on nicotine-induced relaxations of longitudinal muscle strips of rat gastric fundus. 2 In the presence of 1 microM atropine and 3 microM guanethidine, nicotine (30 microM) induces a fast and sustained relaxation which is partly inhibited by the nitric oxide synthase inhibitors Nomega-nitro-L-arginine (L-NOARG) and Nomega-nitro-L-arginine methyl ester (L-NAME) (both 30 and 100 microM). One microM tetrodotoxin (TTX) completely blocks this nicotine-induced relaxation. 3 High concentrations of guanethidine (> or =10 microM), but not adrenoceptor blockade by the alpha-adrenoceptor antagonist phentolamine in combination with the beta-adrenoceptor antagonist nadolol (both 3 microM), inhibit the nicotine-induced relaxation. 4 Guanethidine (0.1-100 microM) has no effect on relaxations induced by electrical field stimulation (EFS; 1-8 Hz), nitric oxide (NO; 0.01-1 microM), vasoactive intestinal polypeptide (VIP; 0.1-10 nM) or isoprenaline (1-10 nM). 5 We conclude that high concentrations of guanethidine (> or =10 microM) block nicotine-induced NANC relaxations of longitudinal muscle strips of the rat gastric fundus most likely at the level of the nicotinic acetylcholine receptor.
 ...
PMID:Nicotinic acetylcholine receptor blocking effect of guanethidine in the rat gastric fundus. 1055 24

Immunocytochemistry and in situ hybridization revealed abundant secretin expressing cells on duodenal villi with a gradual decrease throughout the small intestines of the rat. They were absent in pancreas, stomach and colon. Secretin caused relaxation of rat intestinal longitudinal muscle in vitro. Studies on colon revealed that the secretin-evoked response was unaffected by apamin, tetrodotoxin, L-NAME, VIP or PACAP pretreatment; secretin itself caused desensitization. Addition of VIP or PACAP when the secretin-evoked relaxation was maximal evoked a further relaxation suggesting the presence of distinct receptors. Secretin causes relaxation via activation of secretin receptors located on the smooth muscle and not via any of the related VIP/PACAP receptors.
 ...
PMID:Expression and motor effects of secretin in small and large intestine of the rat. 1109 Sep 23


<< Previous 1 2 3 4 Next >>