Blockade by 4,4′‐diisothiocyanatostilbene‐2,2′‐disulphonate (DIDS) of P2X‐purinoceptors in rat vas deferens

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Abstract
The possibility of an antagonist effect of 4,4′‐diisothiocyanatostilbene‐2,2′‐disulphonate (DIDS) at P2X‐purinoceptors was studied in rat vas deferens. DIDS reduced contractions elicited by α,β‐methylene ATP 3 μm, IC50 1.6 μm, but did not change contractions elicited by K+ 35 mm. DIDS 3.2 μm slightly shifted the concentration‐response curve of α,β‐methylene ATP to the right and reduced the maximum. DIDS 10 μm markedly decreased and DIDS 32 μm abolished contractions over the entire range of the α,β‐methylene ATP concentration‐response curve. DIDS 32 μm also abolished contractions elicited by ATP but did not change contractions elicited by noradrenaline. The antagonist effect of DIDS was only slowly reversible. The presence of either suramin 320 μm or α,β‐methylene ATP 10 μm during the exposure to DIDS protected the tissue from the long‐lasting blocking effect of DIDS. 4,4′‐Diisothiocyanatodihydrostilbene‐2,2′‐disulphonate (H2DIDS) was equipotent with DIDS whereas several analogues in which one or both of the isothiocyanate residues were replaced were less effective or without effect against α,β‐methylene ATP. DIDS attenuated the purinergic component of neurogenic contractions elicited by electrical field stimulation, IC50 3.9 μm, but did not change the adrenergic component. It is concluded that DIDS causes a selective, long‐lasting, non‐equilibrium blockade of P2X‐purinoceptors in rat vas deferens. Due to this effect it also selectively blocks the purinergic component of neurogenic contractions.