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 nM) 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 microM), indomethacin (10 microM) or tetrodotoxin (0.5 microM) but were greatly reduced by nifedipine (3 microM) and by the absence of K+. PTX could not evoke contractions in the absence of Ca2+ 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 microM) plus nifedipine (3 microM) abolished contractile responses to EFS and greatly reduced the contractile response to PTX. 6. The contractile response to PTX (100 nM) was reduced following exposure of the muscle to alpha, beta-methylene ATP. 7. Exposure to PTX (100 nM) 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.