Substance P abolishes the facilitatory effect of ATP on spontaneous glycine release in neurons of the trigeminal nucleus pars caudalis

Citation
Zm. Wang et al., Substance P abolishes the facilitatory effect of ATP on spontaneous glycine release in neurons of the trigeminal nucleus pars caudalis, J NEUROSC, 21(9), 2001, pp. 2983-2991
Citations number
24
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
0270-6474 → ACNP
Volume
21
Issue
9
Year of publication
2001
Pages
2983 - 2991
Database
ISI
SICI code
0270-6474(20010501)21:9<2983:SPATFE>2.0.ZU;2-T
Abstract
Glycine release was facilitated by the activation of presynaptic ATP recept ors (P-2X-type) in a preparation of dissociated trigeminal nucleus pars cau dalis neurons in which the native synaptic boutons were preserved. The acti on of ATP was completely blocked by substance P (SP) without alteration of the miniature IPSC (mIPSC) amplitude distribution. SP itself had no effect on mIPSC frequency or amplitude. The inhibitory effect of SP on ATP action was blocked by CP99994, indicating that the SP receptors are of the neuroki nin-1 type. The ATP-induced facilitation of the mIPSC frequency was unaffec ted by Cd2+. Moreover, SP did not inhibit the increase in mIPSC frequency i nduced high K+ application, suggesting that SP did not modulate voltage-dep endent calcium channels or subsequent steps in the release process. KT5720 and phorbol 12-myristate 13-acetate did not block SP action, indicat ing that neither the cAMP-protein kinase A nor the protein kinase C pathway mediates the SP effects. However, in the presence of N-(6-aminohexyl)-5-ch loro-1-naphthalene sulphonamide (W-7), SP was no longer able to inhibit the ATP-induced stimulation of mIPSC frequency. 1-[N,O-bis(5-isoquinolinesulfo nyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine also suppressed the SP action, suggesting that SP modulates P-2X receptors via a Ca2+/calmodulin-dependent protein kinase II-mediated pathway. In conventional whole-cell mode, the p resence of W-7 in the patch pipette did not affect the SP inhibitory action . Thus, SP is not likely to be generating its modulation through the produc tion of a retrograde signal (involving calmodulin) from the postsynaptic ce ll to the presynaptic boutons. These results are the first demonstration of the modulation of one presynap tic receptor by another. Because SP inhibits the ATP stimulation of glycine release, SP may play a significant role in hyperalgesia or chronic pain.