Dual effects of neurokinin on calcium channel currents and signal pathways in neonatal rat nucleus tractus solitarius.
Neurokinins, such as substance P (SP), modulate the reflex regulation of cardiovascular and respiratory function in the CNS, particularly in the nucleus tractus solitarius (NTS). There is considerable evidence of the action of SP in the NTS, but the precise effects have not yet been determined. Voltage-dependent Ca2+ channels (VDCCs) serve as crucial mediators of membrane excitability and Ca2+ -dependent functions such as neurotransmitter release, enzyme activity and gene expression. The purpose of this study was to investigate the effects of neurokinins on VDCCs currents (ICa) in the NTS using patch-clamp recording methods. In 142 of 282 neurons, an application of [Sar(9), Met(O(2)11]-substance P (SSP, NK(1) receptor agonist) caused facilitation of L-type I(Ba). Intracellular dialysis of the Galpha(q/11)-protein antibody attenuated the SSP-induced facilitation of I(Ba). In addition, phospholipase C (PLC) inhibitor, protein kinase C (PKC) inhibitor and PKC activator attenuated the SSP-induced the facilitation of I(Ba). In contrast, in 115 of 282 neurons, an application of SSP caused inhibition of N- and P/Q-types I(Ba). Intracellular dialysis of the Gbetagamma-protein antibody attenuated the SSP-induced inhibition of I(Ba). These results indicate that NK(1) receptor facilitates L-type VDCCs via Galpha(q/11)-protein involving PKC in NTS. On the other hand, NK(1) receptor inhibits N- and P/Q-types VDCCs via Galpha(q/11)-protein betagamma subunits in NTS.
Endoh
Takayuki
T
Department of Physiology, Tokyo Dental College, 1-2-2 Masago, Chiba, Japan. tendoh@tdc.ac.jp
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D017552:Solitary Nucleus / Q000166:cytology* / Q000187:drug effects; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D015320:Tachykinins; C062618:substance P, Sar(9)-Met(O2)(11)-; D013373:Substance P