Which mechanisms account for the sensory neuron blocking action of capsaicin on primary afferents in the rat urinary bladder?
In the rat isolated bladder, capsaicin produced a concentration-dependent contraction, shown previously to depend upon transmitter release from peripheral endings of primary afferents. When using low concentrations (30-300 nM) of capsaicin, exposure to a second and third dose of capsaicin produced smaller responses than the first application, although a subsequent challenge with 10 microM capsaicin still elicited a contraction which was not reduced as compared to the response produced by the first exposure to a low dose of capsaicin. Capsaicin also evoked a prompt outflow of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI), taken as a marker for sensory nerve activation. A second or third application of a submaximal concentration of the drug was ineffective, although a subsequent challenge with 1 microM capsaicin was effective. These findings indicate that neuropeptide depletion does not necessarily account for the early stage of capsaicin 'desensitization' of primary afferents.
Maggi
C A
CA
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Astolfi
M
M
Donnerer
J
J
Amann
R
R
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation*
D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin