Muscarinic supersensitivity in the rat urinary bladder after capsaicin pretreatment.
The effects of capsaicin on urinary bladder function have been investigated in adult rats. Ten days after capsaicin treatment immunocytochemical investigations showed a nearly complete disappearance of substance P (SP) and calcitonin gene-related peptide (CGRP) in all parts of the bladder. Recordings of micturition patterns and cytometrical investigations in conscious animals revealed no functional effects of capsaicin treatment. In-vitro experiments showed that the contractile response to substance P was similar before and after capsaicin treatment and CGRP exerted no contractile effects on the urinary bladder in either group of rats. The concentration-response curve to carbachol as well as the frequency-response curve to electrical stimulation were significantly shifted to the left in bladder muscle after capsaicin treatment. However, the maximal responses were similar in control and capsaicin-treated bladders. In the presence of scopolamine the maximal response to electrical stimulation was clearly lower in bladders subjected to capsaicin treatment than in controls. In conclusion, depletion of substance P and CGRP in the rat urinary bladder by capsaicin induced no supersensitivity to these peptides. However, the increased sensitivity to carbachol and to electrical stimulation seen after capsaicin treatment indicates the development of a supersensitivity to muscarinic receptor stimulation. Despite this supersensitivity in vitro no functional effects of capsaicin treatment were found in vivo.
Department of Clinical Pharmacology, University of Lund, Sweden.
A
A
Malmgren
E
E
Ekblad
F
F
Sundler
K E
KE
Andersson
P O
PO
Andersson
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D011976:Receptors, Muscarinic; D013373:Substance P; D002217:Carbachol; D015740:Calcitonin Gene-Related Peptide; D011188:Potassium; D002211:Capsaicin