Differential Effects of the Novel Analgesic, S 12813-4, on the Spinal Release of Substance P- and Calcitonin Gene-related Peptide-like Materials in the Rat

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 1994 Apr 1

PMID 7520130

Citations 1

Authors

E Collin

D Frechilla

M Pohl

S Bourgoin

A Mauborgne

M Hamon

F Cesselin

Affiliations

Soon will be listed here.

Abstract

The possible inhibitory control by the novel analgesic S 12813-4 (3-(2-(4-phenylpiperazine-1-yl)-ethyl)-2-oxo-2,3- dihydrooxazolo(b)pyridine) of spinal neurones containing substance P (SP) and/or calcitonin gene-related peptide (CGRP) was assessed in vitro and in vivo in the rat. S 12813-4 (10 nM-0.1 mM) did not affect the spinal release of CGRP-like material (CGRPLM) but inhibited in a concentration dependent manner the K(+)-evoked overflow of SP-like material (SPLM) from slices of the dorsal half of the rat lumbar enlargement. The inhibitory effect of 10 microM S 12813-4 on SPLM release was not additive with that of Na (0.1 mM), and could be prevented by the alpha 2-adrenoceptor antagonist idazoxan (10 microM). Similarly, idazoxan (10 microM) suppressed the inhibition by intrathecally administered S 12813-4 (10 microM) of the spinal outflow of SPLM in halothane anaesthetized rats whose intrathecal space was perfused with an artificial cerebrospinal fluid. These data suggest that the analgesic effect of S 12813-4 might involve some alpha 2-adrenoreceptor-mediated control of SPLM release within the spinal cord. Whether this control concerns SP-containing primary afferent fibres (presynaptic inhibition) or SP-containing interneurones and/or bulbo-spinal SP-ergic pathways (postsynaptic inhibition) deserves further investigations.

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References

Hokfelt T, Ljungdahl A, Terenius L, Elde R, Nilsson G . Immunohistochemical analysis of peptide pathways possibly related to pain and analgesia: enkephalin and substance P. Proc Natl Acad Sci U S A. 1977; 74(7):3081-5. PMC: 431417. DOI: 10.1073/pnas.74.7.3081. View

Davies J . Effects of tizanidine, eperisone and afloqualone on feline dorsal horn neuronal responses to peripheral cutaneous noxious and innocuous stimuli. Neuropharmacology. 1989; 28(12):1357-62. DOI: 10.1016/0028-3908(89)90010-5. View

Pohl M, Collin E, Bourgoin S, Clot A, Hamon M, Cesselin F . In vivo release of calcitonin gene-related peptide-like material from the cervicotrigeminal area in the rat. Effects of electrical and noxious stimulations of the muzzle. Neuroscience. 1992; 50(3):697-706. DOI: 10.1016/0306-4522(92)90458-e. View

Hughes H, Barr G . Analgesic effects of intrathecally applied noradrenergic compounds in the developing rat: differences due to thermal vs mechanical nociception. Brain Res. 1988; 469(1-2):109-20. DOI: 10.1016/0165-3806(88)90174-5. View

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; 359(1-2):177-82. DOI: 10.1016/0006-8993(85)91426-x. View

Willcockson W, Chung J, Hori Y, Lee K, Willis W . Effects of iontophoretically released amino acids and amines on primate spinothalamic tract cells. J Neurosci. 1984; 4(3):732-40. PMC: 6564826. View

Calvillo O, Ghignone M . Presynaptic effect of clonidine on unmyelinated afferent fibers in the spinal cord of the cat. Neurosci Lett. 1986; 64(3):335-9. DOI: 10.1016/0304-3940(86)90351-4. View

Tiseo P, Adler M, Liu-Chen L . Differential release of substance P and somatostatin in the rat spinal cord in response to noxious cold and heat; effect of dynorphin A(1-17). J Pharmacol Exp Ther. 1990; 252(2):539-45. View

Headley P, Duggan A, Griersmith B . Selective reduction by noradrenaline and 5-hydroxytryptamine of nociceptive responses of cat dorsal horn neurones. Brain Res. 1978; 145(1):185-9. DOI: 10.1016/0006-8993(78)90809-0. View

10.

Collin E, Frechilla D, Pohl M, Bourgoin S, LE Bars D, Hamon M . Opioid control of the release of calcitonin gene-related peptide-like material from the rat spinal cord in vivo. Brain Res. 1993; 609(1-2):211-22. DOI: 10.1016/0006-8993(93)90875-n. View

11.

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; 325(1-2):294-8. DOI: 10.1016/0006-8993(85)90326-9. View

12.

Howe J, Yaksh T, Go V . The effect of unilateral dorsal root ganglionectomies or ventral rhizotomies on alpha 2-adrenoceptor binding to, and the substance P, enkephalin, and neurotensin content of, the cat lumbar spinal cord. Neuroscience. 1987; 21(2):385-94. DOI: 10.1016/0306-4522(87)90129-1. View

13.

Yaksh T, TYCE G . Resting and K+-evoked release of serotonin and norephinephrine in vivo from the rat and cat spinal cord. Brain Res. 1980; 192(1):133-46. DOI: 10.1016/0006-8993(80)91014-8. View

14.

Sullivan A, Dashwood M, Dickenson A . Alpha 2-adrenoceptor modulation of nociception in rat spinal cord: location, effects and interactions with morphine. Eur J Pharmacol. 1987; 138(2):169-77. DOI: 10.1016/0014-2999(87)90430-4. View

15.

Go V, Yaksh T . Release of substance P from the cat spinal cord. J Physiol. 1987; 391:141-67. PMC: 1192207. DOI: 10.1113/jphysiol.1987.sp016731. View

16.

Bourgoin S, Pohl M, Benoliel J, Mauborgne A, Collin E, Hamon M . gamma-Aminobutyric acid, through GABAA receptors, inhibits the potassium-stimulated release of calcitonin gene-related peptide- but not that of substance P-like material from rat spinal cord slices. Brain Res. 1992; 583(1-2):344-8. DOI: 10.1016/s0006-8993(10)80048-4. View

17.

Cesselin F, Bourgoin S, Artaud F, Hamon M . Basic and regulatory mechanisms of in vitro release of Met-enkephalin from the dorsal zone of the rat spinal cord. J Neurochem. 1984; 43(3):763-74. DOI: 10.1111/j.1471-4159.1984.tb12798.x. View

18.

Pohl M, Lombard M, Bourgoin S, Carayon A, Benoliel J, Mauborgne A . Opioid control of the in vitro release of calcitonin gene-related peptide from primary afferent fibres projecting in the rat cervical cord. Neuropeptides. 1989; 14(3):151-9. DOI: 10.1016/0143-4179(89)90039-5. View

19.

Hutchison W, Morton C . Electrical stimulation of primary afferent A fibres does not reduce substance P release in the dorsal horn of the cat. Pain. 1989; 37(3):357-363. DOI: 10.1016/0304-3959(89)90201-7. View

20.

Howe J, Wang J, Yaksh T . Selective antagonism of the antinociceptive effect of intrathecally applied alpha adrenergic agonists by intrathecal prazosin and intrathecal yohimbine. J Pharmacol Exp Ther. 1983; 224(3):552-8. View