Potentiation of 5-HT3 receptor function by the activation of coexistent 5-HT2 receptors in trigeminal ganglion neurons of rats.
5-HT receptor subtypes are widely expressed in primary sensory neurons, yet so far little is known about the interaction among them. This study aimed to investigate whether the activation of 5-HT2 and 5-HT1 receptors could modulate 5-HT3 receptor mediated current in rat trigeminal ganglion (TG) neurons using whole-cell patch clamp technique. The majority of TG neurons examined responded to 5-HT (10(-7)-10(-3) M) with a fast activating and rapid desensitizing inward current (77.2%, 71/92). This 5-HT activated current (I(5-HT)) was blocked by ICS 205-930 and mimicked by 2-methyl-5-HT, indicating that it was mediated by 5-HT3 receptor. With alpha-methyl-5-HT applied prior to 5-HT application, I(5-HT) was potentiated in a concentration-dependent manner, with the maximal modulatory effect at 10(-9) M of alpha-methyl-5-HT. The concentration-response curve for I(5-HT) pretreated with alpha-methyl-5-HT shifts upwards compared with that for I(5-HT) without alpha-methyl-5-HT pretreatment, the maximal I(5-HT) value having increased by (60.3 +/- 5.7)% of its control while the EC50 values of the two curves being very close, i.e. (2.0 +/- 0.3) x 10(-5) M vs (1.7 +/- 0.2) x 10(-5) M, respectively. The alpha-methyl-5-HT potentiation of I(5-HT) was removed by intracellular dialysis of either GDP-beta-S, a non-hydrolyzable GDP analog, or GF109203X, a selective PKC inhibitor, almost completely. Preapplication of R-(+)-UH-301, a selective agonist of 5-HT(1A) receptor, had no modulatory effect on I(5-HT). These results suggest that in the membrane of TG neurons, the activation of 5-HT2 receptors can exert an enhancing effect on the function of coexistent 5-HT3 receptors while that of 5-HT(1A) receptors cannot.
Hu
Wang-Ping
WP
Laboratory of Neuropharmacology, Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, PR China.
Guan
Bing-Cai
BC
Ru
Li-Qiang
LQ
Chen
Jian-Guo
JG
Li
Zhi-Wang
ZW
D000818:Animals; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1 / Q000187:drug effects; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects*; D000077526:Tropisetron
D007211:Indoles; D008301:Maleimides; D044402:Receptor, Serotonin, 5-HT2A; D044263:Receptors, Serotonin, 5-HT1; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013873:Thionucleotides; D006153:Guanosine Diphosphate; C042390:alpha-methylserotonin; D012701:Serotonin; D000077526:Tropisetron; C023427:guanosine 5'-O-(2-thiodiphosphate); C070515:bisindolylmaleimide I