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)

1. The effect of the nitric oxide synthase (NOS) inhibitor, 7-nitro indazole (7-NI), on sympathetic and purinergic neurotransmission in the rat isolated vas deferens preparation has been studied. 2. 7-NI (50-200 microM) caused a dose- and frequency-dependent inhibition of the phasic (predominantly purinergic) contractile response of the rat vas deferens to electrical (field) stimulation (100 V, 0.5 ms). Greatest inhibition occurred at lower frequencies of stimulation (0.1-10 Hz). The sustained tonic contractile response (predominantly noradrenergic) was inhibited only at a high frequency of stimulation (60 Hz) and only at the highest concentration of 7-NI studies (200 microM). 3. 7-NI (100 microM) significantly reduced the contractile response of the vas deferens to exogenous ATP (20 microM-5 mM) and the stable P2X purinoceptor agonist, alpha, beta-methylene ATP (2.5 and 25.0 microM) but was without effect on contractions due to noradrenaline (0.1-50 microM) indicating a lack of antagonist effect on post-junctional alpha 1 adrenoceptors. 4. The effect of 7-NI (100 microM) on the phasic contractile response to field stimulation (0.1 and 2.0 Hz) was unaffected by preincubation of preparations with yohimbine (1.0 microM) or propranolol (0.01-10.0 microM) indicating the absence of involvement of alpha 2- or beta-adrenoceptors in this response. 5. 7-NI (50-600 microM) caused dose-related inhibition of contractions elicited by addition of a depolarizing concentration of KCl (64 mM). 6. The effect of 7-NI (100 microM) on the phasic contractile response to field stimulation (0.1 and 2.0 Hz) was unaffected by preincubation of preparations with L-arginine (1 mM). Neither L-arginine (1 mM) nor NC nitro L-arginine methyl ester (L-NAME, 100 LM) affected the response of the vas deferens to field stimulation at 0.1 or 2.0 Hz. Nitric oxide synthase (NOS) enzyme activity, measured as the conversion of[3H]-L-arginine to [3H]-citrulline, was not detectable in rat vas deferens homogenates.7. 7-Nr preferentially inhibits the purinergic component of the response of the rat vas deferens to field stimulation. The mechanism of action of 7-NI is not known but is not related to NOS inhibition. It seems likely that 7-NI combines an antagonist action at smooth muscle cell P2X-purinoceptors with the ability to inhibit the cellular influx of calcium ions. Although these hitherto unrecorded effects of 7-NI occur at relatively high concentrations, the effects described may contribute to the pharmacological effects of this NOS inhibitor.
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PMID:Effect of 7-nitro indazole on neurotransmission in the rat vas deferens: mechanisms unrelated to inhibition of nitric oxide synthase. 752 12

Non-adrenergic, non-cholinergic (NANC) inhibitory neurotransmission has been an area of intense interest in gut motor physiology, whereas excitatory NANC neurotransmission has received less attention. In order to further explore excitatory NANC neurotransmission, we performed conventional intracellular recordings from guinea-pig taenia caeci smooth muscle. Tissue was perfused with oxygenated Krebs solution at 35 degrees C and nerve responses evoked by either oral or aboral nerve stimulation (NS) (4 square wave pulses, 0.3 ms duration, 20 Hz). Electrical activity was characterized by slow waves upon which one to three action potentials were superimposed. Oral NS evoked an inhibitory junction potential (IJP) at either the valley or peak of the slow wave. Application of nifedipine (1 microM) abolished slow waves and action potentials, but membrane potential flunctuations (1-3 mV) and IJPs remained unaffected. Concomitant application of apamin (300 nM), a small-conductance Ca(2+)-activated K(+) channel blocker, converted the IJP to an EJP that was followed by slow IJP. Further administration of N(G)-nitro-l-arginine methyl ester (l-NAME, 200 microM), a nitric oxide synthase inhibitor, abolished the slow IJP without affecting the EJP, implying that the slow IJP is due to nitrergic innervation. The EJP was abolished by tetrodotoxin (1 microM), but was not significantly affected by atropine (3 microM) and guanethidine (3 microM) or hexamethonium (500 microM). Substance P (SP, 1 microM) desensitization caused slight attenuation of the EJP, but the EJP was abolished by desensitization with alpha,beta-methylene ATP (50 microM), a P2 purinoceptor agonist that is more potent than ATP at the P2X receptor subtype, suramin (100 microM), a non-selective P2 purinoceptor antagonist, and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 100 microM) , a selective P2X purinoceptor antagonist. In contrast, the EJP was unaffected by MRS-2179 (2 microM), a selective P2Y(1) receptor antagonist. Aboral NS evoked an apamin- and l-NAME-sensitive IJP, but virtually no NANC EJP. These data suggest the presence of polarized excitatory purinergic neurotransmission in guinea-pig taenia caeci, which appears to be mediated by P2X purinoceptors, most likely the P2X(1) subtype.
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PMID:Excitatory purinergic neurotransmission in smooth muscle of guinea-pig [corrected] taenia caeci. 1567 92