The effects of uranyl ions on neuromuscular transmission in the urinary bladder of the normal and streptozotocin-diabetic mouse.
The depressant effects of uranyl nitrate on the nerve-evoked muscle contraction of urinary bladder isolated from normal and streptozotocin-diabetic mice were compared. The non-cholinergic component of the evoked bladder contraction (in the presence of atropine) was specifically sensitive to the suppressive effect of uranyl nitrate. In contrast, the cholinergic component remaining after treatment with alpha, beta-methylene ATP was rather insensitive to uranyl nitrate. The contractile responses induced by KCl, acetylcholine and ATP were also not affected by uranyl nitrate, indicating a presynaptic site of action. High Ca2+ and calmodulin inhibitors (trifluoperazine, diltiazem and W7) antagonized the suppressive effects of uranyl ions. These results suggest that the depressant effects of uranyl nitrate is mediated by a reduction of prejunctional non-cholinergic transmitter release through the calcium-calmodulin pathway. In contrast to the normal bladder, the urinary bladder of streptozotocin-diabetic mice revealed not only weaker neurogenic contractile responses to electrical field stimulation, but also a profound reduction in the depressant effect of uranyl nitrate. These findings suggest that the Ca2+ regulation of non-cholinergic neurotransmission in mouse urinary bladder may be impaired in the diabetic state.
Liu
S H
SH
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lin-Shiau
S Y
SY
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers; D013311:Streptozocin; D009435:Synaptic Transmission / Q000187:drug effects*; D014502:Uranyl Nitrate / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology
D026902:Potassium Channel Blockers; D014502:Uranyl Nitrate; D013311:Streptozocin