HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 90/1/21    most recent 00108.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (16) Citing Articles via Google Scholar Google Scholar Articles by Sculptoreanu, A. Articles by de Groat, W. C. Search for Related Content PubMed PubMed Citation Articles by Sculptoreanu, A. Articles by de Groat, W. C.

Protein Kinase C Is Involved in Neurokinin Receptor Modulation of N- and L-Type Ca²⁺ Channels in DRG Neurons of the Adult Rat

Department of Pharmacology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15261

Submitted 5 February 2003; accepted in final form 21 March 2003

Whole cell patch-clamp techniques were used to examine neurokinin receptor modulation of Ca²⁺ channels in small to medium size dorsal root ganglia neurons (<40 pF) that express mainly N- and L-type Ca²⁺ currents. Low concentrations of substance P enhanced Ca²⁺ currents (5–40%, <0.2 µM), while higher concentrations applied cumulatively reversed these enhancements (5–28% reductions, >0.5 µM). This apparent inhibition by high concentrations of substance P was blocked by the administration of the NK₃ antagonist SB 235,375 (0.2 µM). The NK₁ agonist, [Sar⁹,Met¹¹]-substance P (0.05 to 1.0 µM) did not alter Ca²⁺ currents; whereas the NK₂ agonist, [Ala⁸]-neurokinin A (4–10), enhanced Ca²⁺ currents (5–36% increase, 0.05–0.5 µM). The enhancement was reversed by the NK₂ antagonist MEN 10,376 (0.2 µM) but unaffected by the NK₃ antagonist SB 235,375 (0.2 µM). The NK₃ agonist [MePhe⁷]-neurokinin B (0.5–1.0 µM) inhibited Ca²⁺ currents (6–24% decrease). This inhibition was not prevented by the NK₂ antagonist MEN 10,376 (0.2 µM) but was blocked by the NK₃ antagonist SB 235,375 (0.2 µM). Both the enhancement and inhibition of Ca²⁺ currents by neurokinin agonists were reversed by the protein kinase C inhibitor bisindolylmaleimide I HCl (0.2–0.5 µM). Following inhibition of Ca²⁺ channels by [MePhe⁷]-neurokinin the facilitatory effect of BayK 8644 (5 µM) was increased and the inhibitory effect of the N-type Ca²⁺ channel blocker w -conotoxin GVIA (1 µM) was diminished, suggesting that the NK₃ agonist inhibits N-type Ca²⁺ channels. Similarly, block of all but N-type Ca²⁺ channels, revealed that [Ala⁸]-neurokinin A (4–10) enhanced the currents while [MePhe⁷]-neurokinin B inhibited the currents. Inhibition of all but L-type Ca²⁺ channels, revealed that [Ala⁸]-neurokinin A (4–10) enhanced the currents while [MePhe⁷]-neurokinin B had no effect. Activation of protein kinase C with low concentrations of phorbol-12,13-dibutyrate enhanced Ca²⁺ currents, but high concentrations inhibited N- and L-type Ca²⁺ currents. In summary, these data suggest that in adult rat dorsal root ganglia neurons, NK₂ receptors enhance both L- and N-type Ca²⁺ channels and NK₃ receptors inhibit N-type Ca²⁺ channels and that these effects are mediated by protein kinase C phosphorylation of Ca²⁺ channels.

This article has been cited by other articles:

				B. Salthun-Lassalle, S. Traver, E. C. Hirsch, and P. P. Michel Substance P, Neurokinins A and B, and Synthetic Tachykinin Peptides Protect Mesencephalic Dopaminergic Neurons in Culture via an Activity-Dependent Mechanism Mol. Pharmacol., November 1, 2005; 68(5): 1214 - 1224. [Abstract] [Full Text] [PDF]

				M. Pieri, C. Severini, G. Amadoro, I. Carunchio, C. Barbato, M. T. Ciotti, and C. Zona AMPA Receptors Are Modulated by Tachykinins in Rat Cerebellum Neurons J Neurophysiol, October 1, 2005; 94(4): 2484 - 2490. [Abstract] [Full Text] [PDF]

				K. Vijayaragavan, M. Boutjdir, and M. Chahine Modulation of Nav1.7 and Nav1.8 Peripheral Nerve Sodium Channels by Protein Kinase A and Protein Kinase C J Neurophysiol, April 1, 2004; 91(4): 1556 - 1569. [Abstract] [Full Text] [PDF]