Project/Area Number |
10672084
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biological pharmacy
|
Research Institution | Fukuoka University |
Principal Investigator |
TAKANO Yukio Fac. Pharm. Sci., Fukuoka University, Associate. Prof., 薬学部, 助教授 (50113246)
|
Co-Investigator(Kenkyū-buntansha) |
HONDA Kenji Fac. Pharm. Sci., Fukuoka University, Assist. Prof., 薬学部, 助手 (60140761)
SAITO Ryo Fac. Pharm. Sci., Fukuoka University, Assist. Prof, 薬学部, 助手 (80122696)
|
Project Period (FY) |
1998 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
Keywords | Tachykinin receptors / Vasopressin receptor / Baroreceptor Roflex / Area postrema / Nucleus tractus soli tarii (NTS) / V1受容体 / 循環調節 / 嘔吐 / バソプレシン / Vi受容体 |
Research Abstract |
1. Role of the area postrema in the arterial baroreceptor reflex of rats In this project, we examined the synaptic connection to the nucleus tractus solitarius (NTS) from the area postrema (AP). We examined that the effects of glutamate receptor antagonists on the responses of NTS neurons to AP stimulation. The action potentials in the NTS were produced by AP stimulation at 0.2 Hz. These action potentials were blocked by a low Ca^<2+> and a high Mg^<2+> solution or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) at 10^<-5> M, but not by DL-2-amino-5-phsphonovaleric acid (AP-5) at 10^<-5> M.Judging from the response time, some NTS neurons may be innervated directly by nerve terminals of AP neurons. These results indicate that the excitation by vasopressin of AP neurons mediated V1 receptors is conveyed to NTS by glutamate via NMDA and non-NMDA receptors, or non-NMDA receptors only. 2. Role of the area postrema in emesis. The emetic response is a defense mechanism which is extremely complicated. Vomiting is a reflex that integrates the visceral afferent and efferent pathways at the vomiting center, which is considered to be situated in the medulla oblongata. Using immunohistochemical techniques, the presence of substance P-containing nerve fibers involved in emesis in the rats and humans has been demonstrated. We observed the localization of tachykininNK-1 receptors in these areas in an auto radiographic receptor binding study using ^3H-substance P as a binding ligand in ferrets. The emetic response induced by either morphine or copper sulphate was suppressed by the microinjection of NK-1 receptor antagonists, HSP-117 (1.0 μg) and CP-99,994 (7.5 μg), into the AP of ferrets. These results show that the NK-1 receptors in the AP, NTS and the dorsal motor nucleus of the vagus may be involved in the mechanisms of emesis.
|