Capsaicin-induced stimulation of polymodal nociceptors is antagonized by ruthenium red independently of extracellular calcium.
The dual effect of capsaicin on primary afferent neurons, excitation and stimulation of transmitter release, its dependence on extracellular calcium and its modulation by Ruthenium Red have been investigated in the rabbit ear. Injection of capsaicin into the central artery of the isolated perfused ear with intact neuronal connection induced a reflex fall in systemic arterial blood pressure of the anaesthetized rabbit. Addition of Ruthenium Red (0.6-20 microM) to the perfusate of the ear reversibly attenuated this response in a dose-dependent manner. Perfusion of the ear with a Ca2+-free, 3 mM EGTA-containing physiological salt solution enhanced the capsaicin-evoked depressor reflex but did not prevent the inhibitory action of Ruthenium Red. Perfusion of the isolated rabbit ear with capsaicin (10 microM)-containing physiological salt solution induced the release of substance P-like immunoreactivity which was inhibited by Ruthenium Red (0.6-20 microM) and by omission of extracellular Ca2+. The results demonstrate that capsaicin-evoked transmitter release is dependent on extracellular calcium while capsaicin-evoked excitation is not reduced in a Ca2+-free perfusate. Both effects of capsaicin are potently inhibited by Ruthenium Red. The fact that capsaicin-induced excitation of primary afferents is antagonized by Ruthenium Red also in the absence of extracellular Ca2+ suggests this inhibitory action of Ruthenium Red is not only mediated by inhibition of transmembrane Ca2+ fluxes.
Amann
R
R
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
Donnerer
J
J
Lembeck
F
F
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology*; D004423:Ear / Q000294:innervation; D066298:In Vitro Techniques; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011817:Rabbits; D012428:Ruthenium / Q000494:pharmacology*; D012430:Ruthenium Red / Q000494:pharmacology*; D013373:Substance P / Q000378:metabolism*
D012430:Ruthenium Red; D013373:Substance P; D012428:Ruthenium; D002211:Capsaicin; D002118:Calcium