In
cyclophosphamide-induced
cystitis in the rat, detrusor function is impaired and the expression and effects of
muscarinic receptors altered. Whether or not the neuronal transmission may be affected by
cystitis was presently investigated. Responses of urinary strip preparations from control and
cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of
muscarinic,
adrenergic and
purinergic receptor antagonists. Generally,
atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types,
purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (
alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The
muscarinic receptor antagonists
atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)/M(3)/M(5)-selective'),
methoctramine ('M(2)-selective') and
pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component.
4-DAMP inhibited the tonic contractions in controls more potently than
methoctramine and
pirenzepine. In inflamed preparations, the
muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the
pirenzepine and
4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls,
methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to
carbachol and
ATP were the same in inflamed and in control strips when related to a reference
potassium response,
isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in
cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-
adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory
muscarinic receptors may be increased.