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Interaction of M3 receptors and calcium channels in feline bladder smooth muscle.

It is known that muscarinic receptors and calcium channels play roles in smooth muscle contraction, but it is unclear which receptor and which calcium channel types are most important. Recent studies have shown that M3 receptors may have a direct interaction with L‐type calcium channels. It is hypothesized that if stimulus evoked activation of muscarinic M3 receptors causes an influx of extracellular calcium by opening of L‐type calcium channels, then administration of L‐type calcium channel inhibitors will attenuate evoked contractions of bladder smooth muscle. This hypothesis was tested using an M3 specific antagonist, DAU 5884 (DAU), and an L‐type calcium channel inhibitor, verapamil (Ver). Using an anesthetized cat model, bladder contractions, evoked by pelvic nerve stimulation (PNS) and exogenous administration of acetylcholine, ATP or beta, gamma methylene ATP (APPCP), before and after administration of DAU, or Ver, were measured using DATAQ data acquisition hardware and software. The results show that DAU decreased cholinergic, but not purinergic contractions. Ver after DAU had no effect on any evoked contractions. Ver alone decreased cholinergic contractions, but not purinergic contractions. DAU after Ver decreased cholinergic, but not purinergic contractions. This data suggests that there is an interaction between M3 receptors and calcium channels, as indicated by the effect of these agents on cholinergic evoked bladder contractions.