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Purines and pyrimidines are not involved in NANC relaxant responses in the rabbit vaginal wall
Author(s) -
Ziessen Tom,
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.0704898
Subject(s) - suramin , adenosine , pertussis toxin , chemistry , purinergic receptor , endocrinology , guanethidine , medicine , pharmacology , adenosine triphosphate , stimulation , biochemistry , biology , g protein , receptor
Non‐adrenergic non‐cholinergic (NANC) relaxant responses were elicited by electrical field stimulation (EFS) in rabbit vaginal wall strips after treatment with guanethidine and scopolamine and raising smooth muscle tone with phenylephrine. Under these conditions treatment with NOS inhibitors revealed a non‐nitrergic NANC relaxant response. The possible role of purines and pyrimidines in these non‐nitrergic NANC responses was investigated. Exogenous application of ATP, ADP, adenosine, UTP, or UDP (all at 0.03–10 m M ) induced concentration‐dependent relaxant responses. Responses to exogenous application of ATP were reduced by the general P2 antagonist cibacron blue (500 μ M ), but not by suramin (100 μ M ) and were unaffected by L ‐NAME (500 μ M ), ω‐conotoxin GVIA (ω‐CTX, 500 n M ) or tetrodotoxin (TTX, 1 μ M ). Responses to exogenous application of adenosine were reduced by the A 2A antagonist ZM‐241385 (30 μ M ). ATP‐ and ADP‐induced responses were unaffected by the G‐protein inhibitor pertussis toxin (100 ng ml −1 ), whilst ADP‐ but not ATP‐induced responses were reduced by GDPβS (100 μ M ), which stabilizes G‐proteins in their inactive state. EFS‐induced non‐nitrergic NANC relaxant responses were unaffected by suramin, cibacron blue, ZM‐241385, pertussis toxin or GDPβS, but were completely inhibited by TTX. Exogenous application of ATP (10 m M ) and adenosine (10 m M ) increased intracellular cyclic adenosine‐3′, 5′‐monophosphate (cAMP). However, non‐nitrergic NANC responses were not associated with increased cAMP. Neither non‐nitrergic NANC responses nor responses to ATP or adenosine were associated with increased intracellular cyclic guanosine‐3′, 5′‐monophosphate (cGMP) concentrations. These results suggest that adenosine A 2A receptors and P2 receptors are present in the rabbit vaginal wall, but that they are not involved in non‐nitrergic NANC relaxant responses.British Journal of Pharmacology (2002) 137 , 513–521. doi: 10.1038/sj.bjp.0704898