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)

The P(2)-purinoceptor antagonist, suramin, was used to investigate the possible involvement of adenosine 5'-triphosphate (ATP) in the inhibitory non-adrenergic non-cholinergic (NANC) innervation of the rat gastric fundus. ATP (1-30 microM) produced biphasic responses consisting of concentration-dependent relaxations followed by concentration-dependent contractions. Suramin (200 microM) significantly reduced relaxations and abolished contractions to ATP. Under NANC conditions, electrical field stimulation (EFS) induced frequency-dependent relaxations. Suramin (200 microM) and the peptidase alpha-chymotrypsin (1 u ml(-1)) had the same effects on EFS-induced relaxations: their duration was reduced, but their magnitude was unaffected. Cumulative relaxations to vasoactive intestinal peptide (VIP; 0.1-100 nM), and to the VIP analogue pituitary adenylate cyclase activating peptide 1-27 (PACAP; 0.2-100 nM), were almost completely abolished by alpha-chymotrypsin (1 u ml(-1)), and were inhibited by suramin (3-200 microM) in an apparently competitive manner. Schild plot analysis indicated that suramin had pA(2) values of 5.1+/-0.2 (Hill slope=0.9+/-0.2) and 5.6+/-0.1 (Hill slope=1.0+/-0.1), against VIP and PACAP, respectively. Concentration-dependent relaxations to nitric oxide (1-30 microM) and cumulative relaxations to isoprenaline (0.1-300 nM) were not affected by suramin (200 microM). No conclusions can be made regarding the possible involvement of ATP in EFS-induced NANC relaxations. The results suggest that suramin acts as a competitive antagonist at VIP receptors in the rat gastric fundus.
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PMID:The P(2)-purinoceptor antagonist suramin is a competitive antagonist at vasoactive intestinal peptide receptors in the rat gastric fundus. 1092 68

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