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 α , β -methylene adenosine-5'-triphosphate ( α , β -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 β -adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased.The contraction of the urinary bladder is principally mediated by the parasympathetic stimulation of the muscarinic receptors populating the detrusor [1]. However, a well-known phenomenon in the rat as well as in many other species is that a large part of the parasympathetic contraction of the bladder is resistant to atropine [2,3]. One non-adrenergic, non-cholinergic transmitter candidate in the atropine-resistant contractile response in the rat bladder is adenosine-5'-triphosphate (ATP, [4 -7]), and in this species the purine generates a transient contraction of the bladder by the activation of P 2X purinoceptors, causing depolarization through non-selective cation channels [8][9][10]. Studies show that in the human urinary bladder, the atropine-resistant contractile response is minute or absent [11][12][13][14], but it may appear in the unstable bladder, during interstitial cystitis or due to spinal cord injuries [15][16][17]. Under such pathological conditions of the bladder, cha...
