Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 May;118(1):150–154. doi: 10.1111/j.1476-5381.1996.tb15378.x

Spinal 5-HT2 receptor-mediated facilitation of pudendal nerve reflexes in the anaesthetized cat.

H Danuser 1, K B Thor 1
PMCID: PMC1909481  PMID: 8733588

Abstract

1. 5-Hydroxytryptamine (5-HT) is intimately associated with central sympathetic and somatic control of the lower urinary tract. The sympathetic and somatic innervation of the lower urinary tract is conveyed through efferent axons of the hypogastric and pudendal nerves, respectively. 2. The present study examined the effects of 2,5-dimethoxy-4-iodophenylisopropylamine (DOI), a 5-HT2 receptor subtype-selective agonist, on evoked potentials recorded from the central ends of the hypogastric and pudendal nerves in response to electrical stimulation of afferent fibres in the pelvic and pudendal nerves, respectively. Various spinalization paradigms were employed to localize the site of action. All cats were pretreated with xylamidine (1 mg kg-1), a peripherally-restricted 5-HT2 receptor antagonist. 3. In acute spinal cats, DOI (0.01-3 mg kg-1, i.v.) reliably produced dose-dependent increases in the pudendal nerve reflex (to 228 +/- 31% of control). These increases were reversed by the 5-HT2 receptor-selective antagonist, LY53857 (0.3-3 mg kg-1, i.v.). On the other hand, in spinally-intact cats, DOI produced no significant changes in the pudendal reflex. However, within minutes of spinalization of DOI-pretreated cats, a marked increase (to 221 +/- 16% of control) in the pudendal reflex was observed which could be reversed by LY53857. No significant effects were observed on hypogastric reflexes in either acute spinal or spinally-intact cats following DOI administration. No effects were seen in either spinally-intact or acute spinal animals when LY53857 was administered as the initial drug. 4. These results indicate that activation of spinal 5-HT2 receptors facilitates pudendal reflexes. In spinally-intact cats, it is hypothesized that DOI activates supraspinal pathways that mediate inhibition of the pudendal reflexes and counteracts the facilitatory effects of spinal 5-HT2 receptor activation.

Full text

PDF
150

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alper R. H., Snider J. M. Activation of serotonin2 (5-HT2) receptors by quipazine increases arterial pressure and renin secretion in conscious rats. J Pharmacol Exp Ther. 1987 Dec;243(3):829–833. [PubMed] [Google Scholar]
  2. Cohen M. L., Fuller R. W., Kurz K. D. LY53857, a selective and potent serotonergic (5-HT2) receptor antagonist, does not lower blood pressure in the spontaneously hypertensive rat. J Pharmacol Exp Ther. 1983 Nov;227(2):327–332. [PubMed] [Google Scholar]
  3. Dabiré H., Chaouche-Teyara K., Cherqui C., Fournier B., Laubie M., Schmitt H. Characterization of DOI, a putative 5-HT2 receptor agonist in the rat. Eur J Pharmacol. 1989 Sep 22;168(3):369–374. doi: 10.1016/0014-2999(89)90799-1. [DOI] [PubMed] [Google Scholar]
  4. Danuser H., Bemis K., Thor K. B. Pharmacological analysis of the noradrenergic control of central sympathetic and somatic reflexes controlling the lower urinary tract in the anesthetized cat. J Pharmacol Exp Ther. 1995 Aug;274(2):820–825. [PubMed] [Google Scholar]
  5. Danuser H., Thor K. B. Inhibition of central sympathetic and somatic outflow to the lower urinary tract of the cat by the alpha 1 adrenergic receptor antagonist prazosin. J Urol. 1995 Apr;153(4):1308–1312. [PubMed] [Google Scholar]
  6. De Groat W. C., Lalley P. M. Reflex firing in the lumbar sympathetic outflow to activation of vesical afferent fibres. J Physiol. 1972 Oct;226(2):289–309. doi: 10.1113/jphysiol.1972.sp009985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. De Groat W. C., Ryall R. W. An excitatory action 0f 5-hydroxytryptamine on sympathetic preganglionic neurones. Exp Brain Res. 1967;3(4):299–305. doi: 10.1007/BF00237556. [DOI] [PubMed] [Google Scholar]
  8. Downie J. W., Bialik G. J. Evidence for a spinal site of action of clonidine on somatic and viscerosomatic reflex activity evoked on the pudendal nerve in cats. J Pharmacol Exp Ther. 1988 Jul;246(1):352–358. [PubMed] [Google Scholar]
  9. Downie J. W., Espey M. J., Gajewski J. B. Alpha 2-adrenoceptors not imidazole receptors mediate depression of a sacral spinal reflex in the cat. Eur J Pharmacol. 1991 Mar 26;195(2):301–304. doi: 10.1016/0014-2999(91)90551-z. [DOI] [PubMed] [Google Scholar]
  10. Fuller R. W., Kurz K. D., Mason N. R., Cohen M. L. Antagonism of a peripheral vascular but not an apparently central serotonergic response by xylamidine and BW 501C67. Eur J Pharmacol. 1986 Jun 5;125(1):71–77. doi: 10.1016/0014-2999(86)90084-1. [DOI] [PubMed] [Google Scholar]
  11. Helke C. J., Thor K. B., Phillips E. T. 5-Hydroxytryptamine1C/2 agonists in the thoracic spinal cord: cardiovascular effects and binding sites in the intermediolateral cell column. J Pharmacol Exp Ther. 1991 Dec;259(3):1335–1343. [PubMed] [Google Scholar]
  12. Helton L. A., Thor K. B., Baez M. 5-hydroxytryptamine2A, 5-hydroxytryptamine2B, and 5-hydroxytryptamine2C receptor mRNA expression in the spinal cord of rat, cat, monkey and human. Neuroreport. 1994 Dec 20;5(18):2617–2620. doi: 10.1097/00001756-199412000-00053. [DOI] [PubMed] [Google Scholar]
  13. Hosoya Y., Okado N., Sugiura Y., Kohno K. Coincidence of "ladder-like patterns" in distributions of monoaminergic terminals and sympathetic preganglionic neurons in the rat spinal cord. Exp Brain Res. 1991;86(1):224–228. doi: 10.1007/BF00231058. [DOI] [PubMed] [Google Scholar]
  14. Hoyer D., Clarke D. E., Fozard J. R., Hartig P. R., Martin G. R., Mylecharane E. J., Saxena P. R., Humphrey P. P. International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol Rev. 1994 Jun;46(2):157–203. [PubMed] [Google Scholar]
  15. Kojima M., Takeuchi Y., Goto M., Sano Y. Immunohistochemical study on the distribution of serotonin fibers in the spinal cord of the dog. Cell Tissue Res. 1982;226(3):477–491. doi: 10.1007/BF00214778. [DOI] [PubMed] [Google Scholar]
  16. Kojima M., Takeuchi Y., Goto M., Sano Y. Immunohistochemical study on the localization of serotonin fibers and terminals in the spinal cord of the monkey (Macaca fuscata). Cell Tissue Res. 1983;229(1):23–36. doi: 10.1007/BF00217878. [DOI] [PubMed] [Google Scholar]
  17. Krier J., Thor K. B., de Groat W. C. Effects of clonidine on the lumbar sympathetic pathways to the large intestine and urinary bladder of the cat. Eur J Pharmacol. 1979 Oct 26;59(1-2):47–53. doi: 10.1016/0014-2999(79)90023-2. [DOI] [PubMed] [Google Scholar]
  18. Lewis D. I., Coote J. H. The influence of 5-hydroxytryptamine agonists and antagonists on identified sympathetic preganglionic neurones in the rat, in vivo. Br J Pharmacol. 1990 Apr;99(4):667–672. doi: 10.1111/j.1476-5381.1990.tb12987.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mawson C., Whittington H. Evaluation of the peripheral and central antagonistic activities against 5-hydroxytryptamine of some new agents. Br J Pharmacol. 1970 May;39(1):223P–224P. [PMC free article] [PubMed] [Google Scholar]
  20. McCall R. B., Aghajanian G. K. Serotonergic facilitation of facial motoneuron excitation. Brain Res. 1979 Jun 15;169(1):11–27. doi: 10.1016/0006-8993(79)90370-6. [DOI] [PubMed] [Google Scholar]
  21. McCall R. B. Evidence for a serotonergically mediated sympathoexcitatory response to stimulation of medullary raphe nuclei. Brain Res. 1984 Oct 8;311(1):131–139. doi: 10.1016/0006-8993(84)91405-7. [DOI] [PubMed] [Google Scholar]
  22. Mizukawa K. The segmental detailed topographical distribution of monoaminergic terminals and their pathways in the spinal cord of the cat. Anat Anz. 1980;147(2):125–144. [PubMed] [Google Scholar]
  23. Morgan C., deGroat W. C., Nadelhaft I. The spinal distribution of sympathetic preganglionic and visceral primary afferent neurons that send axons into the hypogastric nerves of the cat. J Comp Neurol. 1986 Jan 1;243(1):23–40. doi: 10.1002/cne.902430104. [DOI] [PubMed] [Google Scholar]
  24. Pérgola P. E., Alper R. H. Effects of central serotonin on autonomic control of heart rate in intact and baroreceptor deficient rats. Brain Res. 1992 Jun 12;582(2):215–220. doi: 10.1016/0006-8993(92)90135-v. [DOI] [PubMed] [Google Scholar]
  25. Rajaofetra N., Passagia J. G., Marlier L., Poulat P., Pellas F., Sandillon F., Verschuere B., Gouy D., Geffard M., Privat A. Serotoninergic, noradrenergic, and peptidergic innervation of Onuf's nucleus of normal and transected spinal cords of baboons (Papio papio). J Comp Neurol. 1992 Apr 1;318(1):1–17. doi: 10.1002/cne.903180102. [DOI] [PubMed] [Google Scholar]
  26. Ramage A. G., Shepheard S. L., Jordan D., Koss M. C. Can the 5-HT2/1c agonist DOI cause differential sympatho-excitation in nerves supplying the heart in anaesthetized cats? J Auton Nerv Syst. 1993 Jan;42(1):53–62. doi: 10.1016/0165-1838(93)90341-q. [DOI] [PubMed] [Google Scholar]
  27. Rampal G., Mignard P. Behaviour of the urethral striated sphincter and of the bladder in the chronic spinal cat. Implications at the Central Nervous System Level. Pflugers Arch. 1975;353(1):33–42. doi: 10.1007/BF00584509. [DOI] [PubMed] [Google Scholar]
  28. Rampal G., Mignard P. Organization of the nervous control of urethral sphincter. A study in the anaesthetized cat with intact central nervous system. Pflugers Arch. 1975;353(1):21–31. doi: 10.1007/BF00584508. [DOI] [PubMed] [Google Scholar]
  29. Rasmussen K., Aghajanian G. K. Serotonin excitation of facial motoneurons: receptor subtype characterization. Synapse. 1990;5(4):324–332. doi: 10.1002/syn.890050409. [DOI] [PubMed] [Google Scholar]
  30. Roberts M. H., Davies M., Girdlestone D., Foster G. A. Effects of 5-hydroxytryptamine agonists and antagonists on the responses of rat spinal motoneurones to raphe obscurus stimulation. Br J Pharmacol. 1988 Oct;95(2):437–448. doi: 10.1111/j.1476-5381.1988.tb11664.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thor K. B., Hisamitsu T., Roppolo J. R., Tuttle P., Nagel J., deGroat W. C. Selective inhibitory effects of ethylketocyclazocine on reflex pathways to the external urethral sphincter of the cat. J Pharmacol Exp Ther. 1989 Mar;248(3):1018–1025. [PubMed] [Google Scholar]
  32. Thor K. B., Hisamitsu T., de Groat W. C. Unmasking of a neonatal somatovesical reflex in adult cats by the serotonin autoreceptor agonist 5-methoxy-N,N-dimethyltryptamine. Brain Res Dev Brain Res. 1990 Jun 1;54(1):35–42. doi: 10.1016/0165-3806(90)90062-4. [DOI] [PubMed] [Google Scholar]
  33. Thor K. B., Katofiasc M. A. Effects of duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, on central neural control of lower urinary tract function in the chloralose-anesthetized female cat. J Pharmacol Exp Ther. 1995 Aug;274(2):1014–1024. [PubMed] [Google Scholar]
  34. Thor K. B., Morgan C., Nadelhaft I., Houston M., De Groat W. C. Organization of afferent and efferent pathways in the pudendal nerve of the female cat. J Comp Neurol. 1989 Oct 8;288(2):263–279. doi: 10.1002/cne.902880206. [DOI] [PubMed] [Google Scholar]
  35. Thor K. B., Nickolaus S., Helke C. J. Autoradiographic localization of 5-hydroxytryptamine1A, 5-hydroxytryptamine1B and 5-hydroxytryptamine1C/2 binding sites in the rat spinal cord. Neuroscience. 1993 Jul;55(1):235–252. doi: 10.1016/0306-4522(93)90469-v. [DOI] [PubMed] [Google Scholar]
  36. Ueyama T., Mizuno N., Nomura S., Konishi A., Itoh K., Arakawa H. Central distribution of afferent and efferent components of the pudendal nerve in cat. J Comp Neurol. 1984 Jan 1;222(1):38–46. doi: 10.1002/cne.902220104. [DOI] [PubMed] [Google Scholar]
  37. White S. R., Neuman R. S. Facilitation of spinal motoneurone excitability by 5-hydroxytryptamine and noradrenaline. Brain Res. 1980 Apr 21;188(1):119–127. doi: 10.1016/0006-8993(80)90561-2. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES