Abstract
An in vitro preparation measuring functional detrusor muscle strength in terms of intravesical bladder pressure (Pves) following in situ nerv stimulation has been developed in urethane-anesthetized guinea pigs. The increase in bladder pressure following pelvic nerve stimulation was abolished by topical lidocaine or tetrodotoxin, suggesting a neurogenic origin for the in vivo contractile response. Cholinergic antagonists (i.v.) decreased the amplitude of the peak pressure response by about 50% at both high (30 Hz) and low (5 Hz) stimulation rates, with a rank order of potency of atropine > propantheline > oxybutynin > hexahydrosiladifenidol > pirenzepine > methoctramine. The P2 purine receptor antagonist, .alpha.,.beta.-methylene ATP (i.v.), antagonized pelvic nerve-stimulated bladder contractions differentially at 5 and 30 Hz. At low frequencies, .alpha.,.beta.-methylene ATP was both more potent (2.5-fold) and more efficacious (-77 compared to -55%.DELTA.) than at 30 Hz. Atropine and .alpha.,.beta.-methylene ATP together completely inhibited the contractile response. Together, the findings indicate that in guinea pigs, urinary bladder contractions induced by pelvic stimulation in vivo may be mediated by both muscarinic and purinergic receptors and that these bladder contractions may be mediated by the M2.beta. subtype rather than by M1 or M2.alpha. muscarinic receptors.

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