Substance P potentiates 5-HT3 receptor-mediated current in rat trigeminal ganglion neurons.
The present study aimed to investigate the interaction between the coexistent SP receptor and 5-HT3 receptor in trigeminal ganglion (TG) neurons using whole-cell patch clamp technique. The majority of the neurons examined responded to 5-HT with an inward current (I5-HT) (78.2%, 79/101) that could be blocked by 5-HT3 receptor antagonist, ICS-205,930. The I5-HT was potentiated by preapplication of SP (10(-10) to 10(-8) M) in most 5-HT-sensitive cells(78.5%, 62/79). Coapplication of SP and GR-82334, antagonist of NK1 receptor, had no enhancing effect on I5-HT. The concentration-response curves for 5-HT with and without SP preapplication show that: (1) the threshold 5-HT concentrations with and without SP preapplication are basically the same, while SP preapplication increased the maximal value of I5-HT by 38.0% of its control; (2) the EC50 values of the curves with and without SP pretreatment are very close, i.e. 1.89 x 10(-5) M and 2.08 x 10(-5) M (P > 0.1; n = 9), respectively. Intracellular dialysis of GDP-beta-S, a non-hydrolyzable GDP analog, and GF-109203X, a selective protein kinase C inhibitor, removed the SP potentiation of I5-HT. These results may offer a clue to understanding the mechanism underlying the generation and/or regulation of peripheral pain caused by tissue damage inflammation, etc.
Hu
Wang-Ping
WP
Department of Molecular and Cellular Neurobiology, Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China.
You
Xing-Hong
XH
Guan
Bing-Cai
BC
Ru
Li-Qiang
LQ
Chen
Jian-Guo
JG
Li
Zhi-Wang
ZW
D000818:Animals; D004357:Drug Synergism; D066298:In Vitro Techniques; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D013373:Substance P