The action of palytoxin on the isolated detrusor muscle of the rat

1 The effects of a coelenterate toxin, palytoxin (PTX) have been studied in the isolated detrusor muscle of the rat. 2 PTX (1–100 n m ) initiated concentration‐dependent contractions of the detrusor; the contraction led to an irreversible tachyphylaxis. Muscle desensitized to PTX continued to respond to acetylcholine (ACh) and excess K + but the contractions were reduced compared to pre‐PTX contractions. 3 Contractions evoked by PTX were not affected by the presence of atropine (10 μ m ), indomethacin (10 μ m ) or tetrodotoxin (0.5 μ m ) but were greatly reduced by nifedipine (3 μ m ) and by the absence of K + . PTX could not evoke contractions in the absence of Ca 2+ or in tissues depolarized by exposure to excess K + . 4 PTX abolished the neurogenic contractile responses to electrical field stimulation (EFS). 5 Combined treatment with atropine (10 μ m ) plus nifedipine (3 μ m ) abolished contractile responses to EFS and greatly reduced the contractile response to PTX. 6 The contractile response to PTX (100 n m ) was reduced following exposure of the muscle to α,β‐methylene ATP. 7 Exposure to PTX (100 n m ) for 1–3 h reduced both the ACh content of the detrusor (by more than 80%), and the immunoreactivity of neuropeptide Y‐containing nerve fibres compared to control. 8 It is concluded that the primary effect of PTX is to promote the release of endogenous motor transmitters, leading to their eventual depletion.