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In vitro characterization of parasympathetic and sympathetic responses in cyclophosphamide-induced cystitis in the rat.

Journal article
Authors Daniel Giglio
Patrik Aronsson
Leif Eriksson
Gunnar Tobin
Published in Basic & clinical pharmacology & toxicology
Volume 100
Issue 2
Pages 96-108
ISSN 1742-7835
Publication year 2007
Published at Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 96-108
Language en
Links www.ncbi.nlm.nih.gov/sites/entrez?D...
Keywords Adenosine Triphosphate, analogs & derivatives, pharmacology, Adrenergic alpha-Antagonists, pharmacology, Adrenergic beta-Antagonists, pharmacology, Animals, Cyclophosphamide, Cystitis, chemically induced, physiopathology, Diamines, pharmacology, Electric Stimulation, Male, Muscarinic Antagonists, pharmacology, Muscle Contraction, drug effects, physiology, Parasympatholytics, pharmacology, Phentolamine, pharmacology, Piperidines, pharmacology, Pirenzepine, pharmacology, Propranolol, pharmacology, Rats, Rats, Sprague-Dawley, Receptors, Purinergic P2, antagonists & inhibitors, Suramin, pharmacology, Sympatholytics, pharmacology, Urinary Bladder, drug effects, physiology, physiopathology
Subject categories Pharmacology

Abstract

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.

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