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Characterization of the non‐nitrergic NANC relaxation responses in the rabbit vaginal wall
Author(s) -
Ziessen Tom,
Moncada Salvador,
Cellek Selim
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704481
Subject(s) - vasoactive intestinal peptide , chemistry , apamin , endocrinology , medicine , adenosine , nitric oxide , nitric oxide synthase , guanosine , arginine , neuropeptide , potassium channel , biochemistry , receptor , amino acid , biology
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 μ M ), N G ‐nitro‐ L ‐arginine (300 μ M ) or N‐iminoethyl‐ L ‐ornithine (500 μ M ) or the selective soluble guanylate cyclase inhibitor 1H‐[1,2,4]oxadiazolo[4,3,‐a]quinoxalin‐1‐one (ODQ, 10 μ M ). 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 μ M ). 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 α‐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 μ M ) or charybdotoxin (100 n M ) 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.British Journal of Pharmacology (2002) 135 , 546–554; doi: 10.1038/sj.bjp.0704481