Purines and pyrimidines are not involved in NANC relaxant responses in the rabbit vaginal wall

Abstract

1. 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. 2. Exogenous application of ATP, ADP, adenosine, UTP, or UDP (all at 0.03-10 mM) induced concentration-dependent relaxant responses. 3. Responses to exogenous application of ATP were reduced by the general P2 antagonist cibacron blue (500 μM), but not by suramin (100 μM) and were unaffected by L-NAME (500 μM), -ω conotoxin GVIA (ω-CTX, 500 nM) or tetrodotoxin (TTX, 1 μM). 4. Responses to exogenous application of adenosine were reduced by the A 2A antagonist ZM-241385 (30 μM). 5. 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 μM), which stabilizes G-proteins in their inactive state. 6. 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. 7. Exogenous application of ATP (10 mM) and adenosine (10 mM) 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. 8. 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.