Summary
(1) Topical administration of Ruthenium Red (10–100 μM in saline) to the serosal surface of the urinary bladder in urethane-anesthetized rats prevented the motor response of the urinary bladder to topical administration of capsaicin and protected the sensory fibers from capsaicin desensitization, but had no effect on the volume-evoked contractions (micturition reflex). At 1 mM increased bladder capacity and decreased amplitude of micturition contraction were observed. (2) At 100 μM, topical Ruthenium Red prevented the blood pressure rise produced by topical administration of capsaicin onto the bladder but did not affect the blood pressure rise produced by sudden bladder distension in spinal rats. (3) After intrathecal administration, Ruthenium Red (80–800 ng/rat) produced a long lasting inhibition of the micturition reflex in urethane-anesthetized rats, this effect being evident in both vehicleor capsaicin- (50 mg/kg s. c. 4 days before) pretreated rats. At 800 ng/rat, intrathecal Ruthenium Red did not affect the blood pressure rise produced by topical administration of capsaicin onto the rat bladder nor that produced by bladder distension. (4) These findings provide further evidence that Ruthenium Red acts quite selectively as a “capsaicin antagonist” preventing both reflex and “efferent” responses activated by peripherally administered capsaicin. By contrast, sensory impulse generation by a natural stimulus such as bladder distension is apparently unaffected by Ruthenium Red. The marked inhibition of the micturition reflex observed after intrathecal administration of Ruthenium Red does probably not involve an interaction with primary afferents in the spinal cord.
Similar content being viewed by others
References
Abelli L, Conte B, Somma V, Maggi CA, Giuliani S, Geppetti P, Alessandri M, Theodorsson E, Meli A (1988) The contribution of capsaicin-sensitive sensory nerves to xylene-induced visceral pain in conscious, freely moving rats. Naunyn-Schmiedeberg's Arch Pharmacol 337:545–551
Amann R, Lembeck F (1989) Ruthenium Red selectively prevents capsaicin-induced stimulation of afferent neurones. Eur J Pharmacol (in press)
Gamse R, Molnar A, Lembeck F (1979) Substance P release from spinal cord slices by capsaicin. Life Sci 25:629–636
Gamse R, Lackner D, Gamse G, Leeman SE (1981a) Effects of capsaicin pretreatment on capsaicin-evoked release of immunoreactive somatostatin and substance P from primary sensory neurons. Naunyn-Schmiedeberg's Arch Pharmacol 316:38–41
Gamse R, Wax A, Zigmond RE, Leeman SE (1981b) Immunoreactive substance P in sympathetic ganglia: distribution and sensitivity toward capsaicin. Neuroscience 6:437–441
Giuliani S, Maggi CA, Meli A (1988) Capsaicin-sensitive afferents in the rat urinary bladder activate a spinal sympathetic cardiovascular reflex. Naunyn-Schmiedeberg's Arch Pharmacol 338:411–416
Holzer P (1988) Local effector function of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides. Neuroscience 24:739–768
Jancsó G, Karcsú S, Kiraly E, Szebeni A, Toth L, Bacsy E, Joo F, Parducz A (1984) Neurotoxin-induced nerve cell degeneration: possible involvement of calcium. Brain Res 295:211–216
Maggi CA, Meli A (1988) The sensory-efferent function of capsaicin-sensitive nerves. Gen Pharmacol 19:1–43
Maggi CA, Santicioli P, Meli A (1984) The effects of capsaicin on rat urinary bladder motility in vivo. Eur J Pharmacol 103:41–50
Maggi CA, Santicioli P, Meli A (1986a) The non-stop transvesical cystometrogram in urethane anaesthetized rats: a simple procedure for quantitative studies on the various phases of the urinary bladder voiding cycle. J Pharmacol Meth 15:157–167
Maggi CA, Giuliani S, Santicioli P, Meli A (1986b) An analysis of factors involved in determining the voiding cycle of the rat urinary bladder. Am J Physiol 251:R250-R256
Maggi CA, Santicioli P, Borsini F, Giuliani S, Meli A (1986c) The role of the capsaicin-sensitive innervation of the rat urinary bladder in the activation of micturition reflex. Naunyn-Schmiedeberg's Arch Pharmacol 332:276–283
Maggi CA, Giuliani S, Santicioli P, Abelli L, Geppetti P, Somma V, Renzi D, Meli A (1987) Species-related variations in the effect of capsaicin on urinary bladder functions: relation to bladder content of substance P-like immunoreactivity. Naunyn-Schmiedeberg's Arch Pharmacol 336:546–555
Maggi CA, Patacchini R, Santicioli P, Lippe ITh, Giuliani S, Geppetti P, Del Bianco E, Selleri S, Meli A (1988a) The effect of omega conotoxin GVIA a peptide modulator of the Ntype voltage sensitive calcium channels, on motor responses produced by activation of efferent and sensory nerves in mammalian smooth muscle. Naunyn-Schmiedeberg's Arch Pharmacol 338:107–113
Maggi CA, Santicioli P, Patacchini R, Geppetti P, Del Bianco E, Meli A (1988b) Calcium and capsaicin-induced substance P release from peripheral terminals of primary sensory neurons. Regul Peptides 22:117
Maggi CA, Santicioli P, Geppetti P, Parlani M, Astolfi A, Pradelles P, Patacchini R, Meli A (1988c) The antagonism induced by Ruthenium Red of the actions of capsaicin on the peripheral terminals of sensory neurons: further studies. Eur J Pharmacol 154:1–10
Maggi CA, Patacchini R, Santicioli P, Giuliani S, Geppetti P, Meli A (1988d) Protective action of Ruthenium Red toward capsaicin desensitization of sensory fibers. Neurosci Lett 88:201–205
Maggi CA, Abelli L, Giuliani S, Santicioli P, Geppetti P, Somma V, Frilli S, Meli A (1988e) The contribution of sensory nerves to xylene-induced cystitis in rats. Neuroscience 26:709–723
Maggi CA, Giuliani S, Conte B, Furio M, Santicioli P, Meli P, Gragnani L, Meli A (1988f) Prostanoids modulate reflex micturition by acting through capsaicin-sensitive afferents. Eur J Pharmacol 145:105–112
Maggi CA, Patacchini R, Giuliani S, Santicioli P, Meli A (1988g) Evidence for two independent modes of activation of the “efferent” function of capsaicin-sensitive nerves. Eur J Pharmacol 156:367–373
Maggi CA, Santicioli P, Geppetti P, Parlani M, Astolfi M, Del Bianco E, Patacchini R, Giuliani S, Meli A (1989a) The effect of calcium free medium and nifedipine on the release of substance P-like immunoreactivity and contractions induced by capsaicin in the isolated guinea-pig and rat bladder. Gen Pharmacol 20:445–456
Maggi CA, Giuliani S, Meli A (1989b) Dermorphin inhibits micturition reflex in rats at a central site of action. J Autonom Nervous Syst 26:11–16
Maggi CA, Patacchini R, Santicioli P, Giuliani S, Del Bianco E, Geppetti P, Meli A (1989) The “efferent” function of capsaicin-sensitive nerves: Ruthenium Red discriminates between different modes of activation. Eur J Pharmacol (in press)
Marsh SJ, Stansfeld CE, Brown DA, Davey R, McCarthy D (1987) The mechanism of action of capsaicin on sensory C-type neurons and their axons in vitro. Neuroscience 23:275–289
Moskowitz MA, Brody M, Liu-Chen LY (1983) In vitro release of immunoreactive substance P from putative afferent nerve endings in bovine pia arachnoid. Neuroscience 9:809–814
Santicioli P, Patacchini R, Maggi CA, Meli A (1987) Exposure to calcium free medium protects sensory fibers by capsaicin desensitization. Neurosci Lett 88:167–170
Szolcsányi J (1984) Capsaicin-sensitive chemoceptive neural system with dual sensory-effect function. In: Chahl LA, Szolcsanyi J, Lembeck F (eds) Antidromic vasodilation and neurogenic inflammation. Akademiai Kiado, Budapest, pp 26–52
Szolcsányi J, Anton F, Reeh PW, Handwerker HO (1988) Selective excitation by capsaicin of mechano-head nociceptors in rat skin. Brain Res 446:262–268
Tapia R, Meza-Ruiz G (1977) Inhibition by ruthenium red of the calcium-dependent release of [3H] GABA in synaptosomal fractions. Brain Res 126:160–166
Tapia R, Arias C (1981) Calcium transport and the release of neurotransmitters: effects of drugs in vivo and in vitro. In: Tapia R, Cotman CW (eds) Regulatory mechanisms of synaptic transmission. Plenum Press, New York, pp 169–186
Tapia R, Meza-Ruiz G, Duran L, Drucker-Colin RR (1976) Convulsions or flaccid paralysis induced by Ruthenium Red depending on route of administration. Brain Res 116:101–109
Tapia R, Arias C, Morales E (1985) Binding of lanthanum ions and ruthenium red to synaptosomes and its effects on neurotransmitter release. J Neurochem 45:1464–1470
Wood JN, Winter J, James IF, Rang HP, Yeats J, Bevan S (1988) Capsaicin-induced ion fluxes in dorsal root ganglion cells in culture. J Neurosci 8:3209–3220
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Maggi, C.A., Giuliani, S. & Meli, A. Effect of ruthenium red on responses mediated by activation of capsaicin-sensitive nerves of the rat urinary bladder. Naunyn-Schmiedeberg's Arch Pharmacol 340, 541–546 (1989). https://doi.org/10.1007/BF00260609
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00260609