Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Electrical field stimulation (EFS)-induced non-adrenergic non-cholinergic (NANC) relaxation responses in the rabbit vaginal wall were investigated. These NANC responses were partially inhibited with the nitric oxide synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME; 500 microM), N(G)-nitro-L-arginine (300 microM) or N-iminoethyl-L-ornithine (500 microM) or the selective soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 10 microM). Application of L-NAME and ODQ concomitantly did not increase the degree of inhibition. L-NAME or ODQ were observed to be more effective at low frequencies. The resistant part of the responses was more pronounced at higher frequencies and was completely inhibited by tetrodotoxin (1 microM). Exogenous application of the peptides vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide (PACAP-27 and PACAP-38), peptide histidine methionine (PHM), peptide histidine valine (PHV), helospectin-I or -II induced a relaxation response. Calcitonin gene-related peptide or substance P did not cause any relaxation. The peptidase alpha-chymotrypsin (type II; 2 units ml(-1)) did not affect non-nitrergic NANC responses, although it did inhibit relaxation responses elicited by exogenous VIP, PACAP-27, PACAP-38, PHM, PHV, helospectin-I or -II. K(+) channel inhibitors apamin (1 microM) or charybdotoxin (100 nM) when used alone or in conjunction did not affect non-nitrergic NANC responses. The non-nitrergic NANC responses were not associated with any increase in intracellular cyclic adenosine-3', 5'-monophosphate (cyclic AMP) or cyclic guanosine-3', 5'-monophosphate (cyclic GMP) concentrations. The peptide-induced relaxations were all associated with increases in cyclic AMP concentrations. These results suggest that a neuronal factor elicits non-nitrergic NANC responses in the rabbit vaginal wall. The identity of this factor remains to be established.
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PMID:Characterization of the non-nitrergic NANC relaxation responses in the rabbit vaginal wall. 1181 90

The present study determined the effects of acetylcholine (ACh) on the L-type Ca(2+) current (I(Ca,L)) stimulated by beta(1)- or beta(2)-adrenergic receptor (AR) agonists in cat atrial myocytes. When isoproterenol (ISO; 0.1 microM) plus the beta(2)-AR antagonist ICI 118,551 (ISO-beta(1)-AR stimulation) or 0.1 microM fenoterol, a beta(2)-AR agonist (FEN-beta(2)-AR stimulation) increased I(Ca,L), ACh (1 microM) inhibited I(Ca,L) by -60 +/- 4 and -63 +/- 6 %, respectively. When ISO plus the beta(1)-AR antagonist atenolol (ISO-beta(2)-AR stimulation) or 1 microM zinterol (ZIN-beta(2)-AR stimulation) increased I(Ca,L), ACh-induced inhibition of I(Ca,L) was significantly smaller, at -21 +/- 3 and -24 +/- 3 %, respectively. L-N(5)-(1-iminoethyl)ornithine (L-NIO, 10 microM), an inhibitor of nitric oxide (NO) synthase, enhanced ACh-induced inhibition of I(Ca,L) when stimulated by ZIN-beta(2)-ARs, but not when stimulated by ISO-beta(1)-ARs or FEN-beta(2)-ARs. Haemoglobin (50 microM), a NO scavenger, also enhanced ACh-induced inhibition when I(Ca,L) was stimulated by ZIN-beta(2)-ARs, but not when stimulated by FEN-beta(2)-ARs. ACh-induced inhibition of I(Ca,L) stimulated by ZIN-beta(2)-ARs was not affected by 10 microM 1H-[1,2,4] oxadiazolo[4,3-a] quinoxaline-1-one (ODQ) a guanylate cyclase inhibitor, but was significantly enhanced by 500 microM reduced glutathione or 100 microM dithiothreitol, agents that act as sinks for S-nitrosylation. ACh-induced inhibition was smaller when I(Ca,L) was stimulated by spermine/NO, a NO donor, than by milrinone, a phosphodiesterase type III inhibitor. ISO (ISO-beta(1)/beta(2)-AR stimulation) increased I(Ca,L) and even though ISO releases NO, ACh prominently inhibited I(Ca,L). This inhibitory effect of ACh was enhanced by L-NIO. Stimulation of ZIN-beta(2)-ARs increased intracellular NO, whereas ISO-beta(1)-ARs or FEN-beta(2)-ARs failed to increase intracellular NO. These results indicate that in atrial myocytes, NO released by selective beta(2)-AR stimulation prevents ACh-induced inhibition of I(Ca,L) stimulated by beta(2)-ARs. NO acts via a cGMP-independent, S-nitrosylation mechanism. Although FEN acts via beta(2)-ARs, it fails to stimulate G(i)-/NO signalling and preferentially stimulates G(s)-/adenylate cyclase signalling, similar to beta(1)-ARs. These findings indicate that NO signalling modulates muscarinic receptor inhibition of atrial function stimulated by beta(2)-ARs.
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PMID:Nitric oxide signalling by selective beta(2)-adrenoceptor stimulation prevents ACh-induced inhibition of beta(2)-stimulated Ca(2+) current in cat atrial myocytes. 1215 73


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