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. 1987 Oct;391:141–167. doi: 10.1113/jphysiol.1987.sp016731

Release of substance P from the cat spinal cord.

V L Go 1, T L Yaksh 1
PMCID: PMC1192207  PMID: 2451003

Abstract

1. The present experiments examine the physiology and pharmacology of the release of substance P-like immunoreactivity (SP-l.i.), from the spinal cord in the halothane-anaesthetized, artificially ventilated cat. 2. Resting release of SP-l.i. was 36 +/- 4 fmol/30 min (mean +/- S.E.; n = 106). Bilateral stimulation of the sciatic nerves at intensities which evoked activity in fibres conducting at A beta conduction velocities (greater than 40 m/s), resulted in no change in blood pressure, pupil diameter or release of SP-l.i. Stimulation intensities which activate fibres conducting at velocities less than 2 m/s resulted in increased blood pressure, miosis and elevated release of SP-l.i. (278 +/- 16% of control). 3. The relationship between nerve-stimulation frequency and release was monotonic up to approximately 20 Hz. Higher stimulation frequencies did not increase the amounts of SP-l.i. released. At 200 Hz there was a reduction. 4. Capsaicin (0.1 mM) increased the release of SP-l.i. from the spinal cord and resulted in an acute desensitization to subsequent nerve stimulation. This acute effect was not accompanied by a reduction in spinal levels of SP-l.i. measured 2 h after stimulation. 5. Cold block of the cervical spinal cord resulted in an increase in the amounts of SP-l.i. released by nerve stimulation. 6. Pre-treatment with intrathecal 5,6-dihydroxytryptamine (300 micrograms) 7 days prior to the experiment caused a reduction in the dorsal and ventral horn stores of SP-l.i., but had no effect on the release of SP-l.i. evoked by nerve stimulation. Similar pre-treatment with intrathecal capsaicin (300 micrograms) resulted in depletion of SP-l.i. in the dorsal but not in the ventral horn of the spinal cord and diminished the release of SP-l.i. evoked by nerve stimulation. 7. Intense thermal stimulation of the flank resulted in small (20-35%), but reliable increases in the release of SP-l.i. above control. 8. Putative agonists for the opioid mu-receptor (morphine, 10-100 microM; sufentanil, 1 microM), and for the delta-receptor (D-Ala2-D-Leu5-enkephalin, 1-10 microM; D-Pen2-D-Pen5-enkephalin, 10 microM), but not the kappa-receptor (U50488H, 100-1000 microM), produced a dose-dependent, naloxone-reversible reduction of the evoked, but not of the resting release of SP-l.i. (-)-Naloxone, but not (+)-naloxone, resulted in a significant increase in evoked but not resting SP-l.i. release.(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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  1. ANGELUCCI L. Experiments with perfused frog's spinal cord. Br J Pharmacol Chemother. 1956 Jun;11(2):161–170. doi: 10.1111/j.1476-5381.1956.tb01047.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Akagi H., Otsuka M., Yanagisawa M. Identification by high-performance liquid chromatography of immunoreactive substance P released from isolated rat spinal cord. Neurosci Lett. 1980 Dec;20(3):259–263. doi: 10.1016/0304-3940(80)90157-3. [DOI] [PubMed] [Google Scholar]
  3. Atweh S. F., Kuhar M. J. Autoradiographic localization of opiate receptors in rat brain. I. Spinal cord and lower medulla. Brain Res. 1977 Mar 18;124(1):53–67. doi: 10.1016/0006-8993(77)90863-0. [DOI] [PubMed] [Google Scholar]
  4. Cuello A. C., Jessell T. M., Kanazawa I., Iversen L. L. Substance P: localization in synaptic vesicles in rat central nervous system. J Neurochem. 1977 Oct;29(4):747–751. doi: 10.1111/j.1471-4159.1977.tb07795.x. [DOI] [PubMed] [Google Scholar]
  5. Dodd J., Jahr C. E., Hamilton P. N., Heath M. J., Matthew W. D., Jessell T. M. Cytochemical and physiological properties of sensory and dorsal horn neurons that transmit cutaneous sensation. Cold Spring Harb Symp Quant Biol. 1983;48(Pt 2):685–695. doi: 10.1101/sqb.1983.048.01.072. [DOI] [PubMed] [Google Scholar]
  6. Duggan A. W., Hendry I. A. Laminar localization of the sites of release of immunoreactive substance P in the dorsal horn with antibody-coated microelectrodes. Neurosci Lett. 1986 Jul 11;68(1):134–140. doi: 10.1016/0304-3940(86)90243-0. [DOI] [PubMed] [Google Scholar]
  7. Dunlap K., Fischbach G. D. Neurotransmitters decrease the calcium conductance activated by depolarization of embryonic chick sensory neurones. J Physiol. 1981 Aug;317:519–535. doi: 10.1113/jphysiol.1981.sp013841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fields H. L., Emson P. C., Leigh B. K., Gilbert R. F., Iversen L. L. Multiple opiate receptor sites on primary afferent fibres. Nature. 1980 Mar 27;284(5754):351–353. doi: 10.1038/284351a0. [DOI] [PubMed] [Google Scholar]
  9. Fitzgerald M. Capsaicin and sensory neurones--a review. Pain. 1983 Feb;15(2):109–130. doi: 10.1016/0304-3959(83)90012-x. [DOI] [PubMed] [Google Scholar]
  10. Fitzgerald M., Woolf C. J. The time course and specificity of the changes in the behavioural and dorsal horn cell responses to noxious stimuli following peripheral nerve capsaicin treatment in the rat. Neuroscience. 1982;7(9):2051–2056. doi: 10.1016/0306-4522(82)90119-1. [DOI] [PubMed] [Google Scholar]
  11. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gamse R., Holzer P., Lembeck F. Indirect evidence for presynaptic location of opiate receptors on chemosensitive primary sensory neurones. Naunyn Schmiedebergs Arch Pharmacol. 1979 Sep;308(3):281–285. doi: 10.1007/BF00501394. [DOI] [PubMed] [Google Scholar]
  13. Gamse R., Lackner D., Gamse G., Leeman S. E. Effect of capsaicin pretreatment on capsaicin-evoked release of immunoreactive somatostatin and substance P from primary sensory neurons. Naunyn Schmiedebergs Arch Pharmacol. 1981 Feb;316(1):38–41. doi: 10.1007/BF00507224. [DOI] [PubMed] [Google Scholar]
  14. Henry J. L. Effects of substance P on functionally identified units in cat spinal cord. Brain Res. 1976 Sep 24;114(3):439–451. doi: 10.1016/0006-8993(76)90965-3. [DOI] [PubMed] [Google Scholar]
  15. Howe J. R., Wang J. Y., Yaksh T. L. Selective antagonism of the antinociceptive effect of intrathecally applied alpha adrenergic agonists by intrathecal prazosin and intrathecal yohimbine. J Pharmacol Exp Ther. 1983 Mar;224(3):552–558. [PubMed] [Google Scholar]
  16. Hökfelt T., Kellerth J. O., Nilsson G., Pernow B. Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons. Brain Res. 1975 Dec 19;100(2):235–252. doi: 10.1016/0006-8993(75)90481-3. [DOI] [PubMed] [Google Scholar]
  17. Hökfelt T., Ljungdahl A., Steinbusch H., Verhofstad A., Nilsson G., Brodin E., Pernow B., Goldstein M. Immunohistochemical evidence of substance P-like immunoreactivity in some 5-hydroxytryptamine-containing neurons in the rat central nervous system. Neuroscience. 1978;3(6):517–538. doi: 10.1016/0306-4522(78)90017-9. [DOI] [PubMed] [Google Scholar]
  18. Jancsó G., Hökfelt T., Lundberg J. M., Kiraly E., Halász N., Nilsson G., Terenius L., Rehfeld J., Steinbusch H., Verhofstad A. Immunohistochemical studies on the effect of capsaicin on spinal and medullary peptide and monoamine neurons using antisera to substance P, gastrin/CCK, somatostatin, VIP, enkephalin, neurotensin and 5-hydroxytryptamine. J Neurocytol. 1981 Dec;10(6):963–980. doi: 10.1007/BF01258524. [DOI] [PubMed] [Google Scholar]
  19. Jeftinija S., Semba K., Randić M. Norepinephrine reduces excitability of single cutaneous primary afferent C-fibers in the cat spinal cord. Brain Res. 1981 Aug 31;219(2):456–463. doi: 10.1016/0006-8993(81)90310-3. [DOI] [PubMed] [Google Scholar]
  20. Jessell T. M., Iversen L. L. Opiate analgesics inhibit substance P release from rat trigeminal nucleus. Nature. 1977 Aug 11;268(5620):549–551. doi: 10.1038/268549a0. [DOI] [PubMed] [Google Scholar]
  21. Jhamandas K., Yaksh T. L., Harty G., Szolcsanyi J., Go V. L. Action of intrathecal capsaicin and its structural analogues on the content and release of spinal substance P: selectivity of action and relationship to analgesia. Brain Res. 1984 Jul 23;306(1-2):215–225. doi: 10.1016/0006-8993(84)90371-8. [DOI] [PubMed] [Google Scholar]
  22. Kaufman M. P., Iwamoto G. A., Longhurst J. C., Mitchell J. H. Effects of capsaicin and bradykinin on afferent fibers with ending in skeletal muscle. Circ Res. 1982 Jan;50(1):133–139. doi: 10.1161/01.res.50.1.133. [DOI] [PubMed] [Google Scholar]
  23. Kuraishi Y., Hirota N., Sato Y., Hino Y., Satoh M., Takagi H. Evidence that substance P and somatostatin transmit separate information related to pain in the spinal dorsal horn. Brain Res. 1985 Jan 28;325(1-2):294–298. doi: 10.1016/0006-8993(85)90326-9. [DOI] [PubMed] [Google Scholar]
  24. Kuraishi Y., Hirota N., Sato Y., Kaneko S., Satoh M., Takagi H. Noradrenergic inhibition of the release of substance P from the primary afferents in the rabbit spinal dorsal horn. Brain Res. 1985 Dec 16;359(1-2):177–182. doi: 10.1016/0006-8993(85)91426-x. [DOI] [PubMed] [Google Scholar]
  25. Kuraishi Y., Hirota N., Sugimoto M., Satoh M., Takagi H. Effects of morphine on noxious stimuli-induced release of substance P from rabbit dorsal horn in vivo. Life Sci. 1983;33 (Suppl 1):693–696. doi: 10.1016/0024-3205(83)90597-0. [DOI] [PubMed] [Google Scholar]
  26. Lahti R. A., VonVoigtlander P. F., Barsuhn C. Properties of a selective kappa agonist, U-50,488H. Life Sci. 1982 Nov 15;31(20-21):2257–2260. doi: 10.1016/0024-3205(82)90132-1. [DOI] [PubMed] [Google Scholar]
  27. Lamotte C., Pert C. B., Snyder S. H. Opiate receptor binding in primate spinal cord: distribution and changes after dorsal root section. Brain Res. 1976 Aug 13;112(2):407–412. doi: 10.1016/0006-8993(76)90296-1. [DOI] [PubMed] [Google Scholar]
  28. Mudge A. W., Leeman S. E., Fischbach G. D. Enkephalin inhibits release of substance P from sensory neurons in culture and decreases action potential duration. Proc Natl Acad Sci U S A. 1979 Jan;76(1):526–530. doi: 10.1073/pnas.76.1.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Murase K., Randić M. Actions of substance P on rat spinal dorsal horn neurones. J Physiol. 1984 Jan;346:203–217. doi: 10.1113/jphysiol.1984.sp015017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Nagy J. I., Hunt S. P. The termination of primary afferents within the rat dorsal horn: evidence for rearrangement following capsaicin treatment. J Comp Neurol. 1983 Aug 1;218(2):145–158. doi: 10.1002/cne.902180203. [DOI] [PubMed] [Google Scholar]
  31. Ninkovic M., Hunt S. P., Gleave J. R. Localization of opiate and histamine H1-receptors in the primate sensory ganglia and spinal cord. Brain Res. 1982 Jun 10;241(2):197–206. doi: 10.1016/0006-8993(82)91056-3. [DOI] [PubMed] [Google Scholar]
  32. Ninkovic M., Hunt S. P., Kelly J. S. Effect of dorsal rhizotomy on the autoradiographic distribution of opiate and neurotensin receptors and neurotensin-like immunoreactivity within the rat spinal cord. Brain Res. 1981 Dec 28;230(1-2):111–119. doi: 10.1016/0006-8993(81)90395-4. [DOI] [PubMed] [Google Scholar]
  33. Otsuka M., Konishi S. Substance P and excitatory transmitter of primary sensory neurons. Cold Spring Harb Symp Quant Biol. 1976;40:135–143. doi: 10.1101/sqb.1976.040.01.015. [DOI] [PubMed] [Google Scholar]
  34. Pang I. H., Vasko M. R. Morphine and norepinephrine but not 5-hydroxytryptamine and gamma-aminobutyric acid inhibit the potassium-stimulated release of substance P from rat spinal cord slices. Brain Res. 1986 Jun 25;376(2):268–279. doi: 10.1016/0006-8993(86)90189-7. [DOI] [PubMed] [Google Scholar]
  35. Reddy S. V., Maderdrut J. L., Yaksh T. L. Spinal cord pharmacology of adrenergic agonist-mediated antinociception. J Pharmacol Exp Ther. 1980 Jun;213(3):525–533. [PubMed] [Google Scholar]
  36. Ruda M. A., Coffield J., Steinbusch H. W. Immunocytochemical analysis of serotonergic axons in laminae I and II of the lumbar spinal cord of the cat. J Neurosci. 1982 Nov;2(11):1660–1671. doi: 10.1523/JNEUROSCI.02-11-01660.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sastry B. R. Potentiation of presynaptic inhibition of nociceptive pathways as a mechanism for analgesia. Can J Physiol Pharmacol. 1980 Jan;58(1):97–101. doi: 10.1139/y80-017. [DOI] [PubMed] [Google Scholar]
  38. Sawynok J., Kato N., Havlicek V., LaBella F. S. Lack of effect of baclofen on substance P and somatostatin release from the spinal cord in vitro. Naunyn Schmiedebergs Arch Pharmacol. 1982 Apr;319(1):78–81. doi: 10.1007/BF00491482. [DOI] [PubMed] [Google Scholar]
  39. Schmauss C., Shimohigashi Y., Jensen T. S., Rodbard D., Yaksh T. L. Studies on spinal opiate receptor pharmacology. III. Analgetic effects of enkephalin dimers as measured by cutaneous-thermal and visceral-chemical evoked responses. Brain Res. 1985 Jul 1;337(2):209–215. doi: 10.1016/0006-8993(85)90056-3. [DOI] [PubMed] [Google Scholar]
  40. Schmauss C., Yaksh T. L. In vivo studies on spinal opiate receptor systems mediating antinociception. II. Pharmacological profiles suggesting a differential association of mu, delta and kappa receptors with visceral chemical and cutaneous thermal stimuli in the rat. J Pharmacol Exp Ther. 1984 Jan;228(1):1–12. [PubMed] [Google Scholar]
  41. Takano Y., Martin J. E., Leeman S. E., Loewy A. D. Substance P immunoreactivity released from rat spinal cord after kainic acid excitation of the ventral medulla oblongata: a correlation with increases in blood pressure. Brain Res. 1984 Jan 16;291(1):168–172. doi: 10.1016/0006-8993(84)90666-8. [DOI] [PubMed] [Google Scholar]
  42. Traynor J. R., Kelly P. D., Rance M. J. Multiple opiate binding sites in rat spinal cord. Life Sci. 1982 Sep 20;31(12-13):1377–1380. doi: 10.1016/0024-3205(82)90385-x. [DOI] [PubMed] [Google Scholar]
  43. Tuchscherer M. M., Seybold V. S. Immunohistochemical studies of substance P, cholecystokinin-octapeptide and somatostatin in dorsal root ganglia of the rat. Neuroscience. 1985 Feb;14(2):593–605. doi: 10.1016/0306-4522(85)90313-6. [DOI] [PubMed] [Google Scholar]
  44. Tyce G. M., Yaksh T. L. Monoamine release from cat spinal cord by somatic stimuli: an intrinsic modulatory system. J Physiol. 1981 May;314:513–529. doi: 10.1113/jphysiol.1981.sp013722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Urbán L., Randić M. Slow excitatory transmission in rat dorsal horn: possible mediation by peptides. Brain Res. 1984 Jan 9;290(2):336–341. doi: 10.1016/0006-8993(84)90952-1. [DOI] [PubMed] [Google Scholar]
  46. Werz M. A., Macdonald R. L. Opioid peptides with differential affinity for mu and delta receptors decrease sensory neuron calcium-dependent action potentials. J Pharmacol Exp Ther. 1983 Nov;227(2):394–402. [PubMed] [Google Scholar]
  47. Williams J. T., Zieglgänsberger W. The acute effects of capsaicin on rat primary afferents and spinal neurons. Brain Res. 1982 Dec 16;253(1-2):125–131. doi: 10.1016/0006-8993(82)90679-5. [DOI] [PubMed] [Google Scholar]
  48. Winter E., Keen P. Effects of synthesis inhibition and nervous activity on concentrations of neuronal substance P. Naunyn Schmiedebergs Arch Pharmacol. 1983 Jun;323(2):173–175. doi: 10.1007/BF00634267. [DOI] [PubMed] [Google Scholar]
  49. Yaksh T. L., Abay E. O., 2nd, Go V. L. Studies on the location and release of cholecystokinin and vasoactive intestinal peptide in rat and cat spinal cord. Brain Res. 1982 Jun 24;242(2):279–290. doi: 10.1016/0006-8993(82)90311-0. [DOI] [PubMed] [Google Scholar]
  50. Yaksh T. L. Analgetic actions of intrathecal opiates in cat and primate. Brain Res. 1978 Sep 15;153(1):205–210. doi: 10.1016/0006-8993(78)91146-0. [DOI] [PubMed] [Google Scholar]
  51. Yaksh T. L., Jessell T. M., Gamse R., Mudge A. W., Leeman S. E. Intrathecal morphine inhibits substance P release from mammalian spinal cord in vivo. Nature. 1980 Jul 10;286(5769):155–157. doi: 10.1038/286155a0. [DOI] [PubMed] [Google Scholar]
  52. Yaksh T. L. Multiple opioid receptor systems in brain and spinal cord: Part 2. Eur J Anaesthesiol. 1984 Sep;1(3):201–243. [PubMed] [Google Scholar]
  53. Yaksh T. L. Multiple opioid receptor systems in brain and spinal cord: Part I. Eur J Anaesthesiol. 1984 Jun;1(2):171–199. [PubMed] [Google Scholar]
  54. Yaksh T. L., Noueihed R. The physiology and pharmacology of spinal opiates. Annu Rev Pharmacol Toxicol. 1985;25:433–462. doi: 10.1146/annurev.pa.25.040185.002245. [DOI] [PubMed] [Google Scholar]
  55. Yaksh T. L. Pharmacology of spinal adrenergic systems which modulate spinal nociceptive processing. Pharmacol Biochem Behav. 1985 May;22(5):845–858. doi: 10.1016/0091-3057(85)90537-4. [DOI] [PubMed] [Google Scholar]
  56. Yaksh T. L., Schmauss C., Micevych P. E., Abay E. O., Go V. L. Pharmacological studies on the application, disposition, and release of neurotensin in the spinal cord. Ann N Y Acad Sci. 1982;400:228–243. doi: 10.1111/j.1749-6632.1982.tb31572.x. [DOI] [PubMed] [Google Scholar]

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