Prejunctional facilitatory and inhibitory modulation of parasympathetic nerve transmission in the rabbit urinary...

Release of [3H]choline and muscle contraction in response to electrical field stimulation were measured from rabbit detrusor muscle strips previously loaded with [3H]choline. The importance of different stimulation frequencies (1 and 10 Hz) for activating either facilitatory or inhibitory prejunctional effects was examined in the presence of muscarinic and adrenergic (alpha2) receptor selective substances. At 1 Hz, neither [3H]choline overflow nor contraction was affected by the M1-selective receptor antagonist pirenzepine (10(-7) M), whereas overflow and contraction decreased at 10 Hz. The M1-selective receptor agonist McN-A-343 (10(-6) M) caused no significant changes except for reducing contractions at 10 Hz. The M2-selective receptor antagonist methoctramine (10(-6) M), on the other hand, increased overflow as well as contraction at both frequencies, most conspicuously at 1 Hz. Atropine (10(-7) M) caused a significant increase with respect to overflow only at 1 Hz, while quite the opposite effect occurred with respect to contractions (reduced only at 10 Hz). Clonidine (10(-6) M) induced inhibition of [3H]choline overflow at 10 Hz only, but without significantly changing contractile responses. The results show that in the rabbit urinary bladder a muscarinic autoreceptor mediated inhibition (M2) of the transmitter release dominates during low frequency stimulation and that a facilitation (M1) may be present at stimulations with higher frequencies. However, this amplification may also be influenced by alpha2-adrenoceptor mediated inhibition.