Tachykinin-like immunoreactivity in the mammalian urinary bladder: correlation with the functions of the capsaicin-sensitive sensory nerves.
The tachykinin-like immunoreactivity of the urinary bladder has been measured in various species by means of an antiserum (K12) having negligible cross-reactivity with substance P. The rank order for bladder content of tachykinin-like immunoreactivity was guinea-pig greater than mice greater than rat, similar to that found for substance P-like immunoreactivity. In all three species, both substance P- and tachykinin-like immunoreactivities were depleted by systemic capsaicin desensitization. The time course for depletion of substance P- and tachykinin-like immunoreactivities of the rat bladder following extrinsic denervation was almost superimposable. At reverse phase high pressure liquid chromatography, the major constituent of tachykinin-like immunoreactivity of the rat bladder co-eluted with neurokinin A. In vitro, the contractile response of the rat bladder to capsaicin (1 microM) was directly proportional to bladder tachykinin-like immunoreactivity while the response to field stimulation was not. In vivo, the volume threshold for reflex micturition was inversely proportional to bladder tachykinin-like immunoreactivity while amplitude of micturition contraction was not. Similar correlations were found in a previous study for substance P-like immunoreactivity. The contractile response to capsaicin or neurokinin A of the rat isolated bladder were significantly reduced by incubation with phenoxybenzamine at a concentration reported to produce a selective alkylation of neurokinin-2 receptors, while the response to substance P or KCl was unaffected. These findings indicate that multiple neurokinins co-exist in those bladder sensory nerves which are capsaicin-sensitive in adult rats. Both substance P- and tachykinin-like immunoreactivities in the rat bladder appear to be good functional markers of the sensory and "efferent" functions mediated by capsaicin-sensitive nerves, consistent with the hypothesis of a transmitter role for the corresponding peptides.
Maggi
C A
CA
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Geppetti
P
P
Santicioli
P
P
Frilli
S
S
Giuliani
S
S
Furio
M
M
Theodorsson
E
E
Fusco
B
B
Meli
A
A
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D015288:Neurokinin A; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013373:Substance P / Q000378:metabolism*; D015320:Tachykinins; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation*
D009479:Neuropeptides; D015320:Tachykinins; D010643:Phenoxybenzamine; D013373:Substance P; D015288:Neurokinin A; D002211:Capsaicin