| Co-Investigator(Kenkyū-buntansha) |
HONDA Kenji Fukuoka Univ., Dept. of Pharmacol., Assistant Prof., 薬学部, 助手 (60140761)
SAITO Ryo Fukuoka Univ., Dept. of Pharmacol., Assistant Prof., 薬学部, 助手 (80122696)
TAKANO Yukio Fukuoka Univ., Dept. of Pharmacol., Assistant Prof., 薬学部, 助手 (50113246)
|
|---|
| Research Abstract |
1. Central cardiovascular regulation of tachykinin peptides.
The central pressor responses due to substance P (SP), neurokinin A (NKA) and neuropeptidegamma (NPgamma) were blocked by sympathetic blocking agents. These results suggest that central SP, NKA and NPgamma, derived from the preprotachykinin A gene, increase the blood pressure (BP) and heart rate via sympathetic nerve activity. In contrast, the pressor response to an neurokinin B (NKB) analogue senktide was inhibited by a vasopressin antagonist, and senktide caused an increase in plasma vasopressin level. In addition, injection of senktide into the paraventricularnucleus (PVN) of the hypothalamus also increased the BP. These results suggest that central NKB, derived from the preprotachykinin B gene, stimulated the NK-3 receptor in the PVN, and increase the BP via release of vasopressin from the pituitary gland.
2. Tachykinin receptor subtype in the endothelial cell and vasodilation.
Agonists for the NK-1 tachykinin receptor elicited the potent, transient and endothelium-dependent relaxation. SP-induced relaxation and increase of cGMP content were inhibited by hemoglobin, methylene blue,L-NG-monomethyl-D-arginine. These results suggest that the relaxation induced by SP is mediated by endothelium-derived relaxingfactor (EDRF). In addition, we examined ^<125>I-SP binding to the endothelial cell membranes of porcine aorta.The cells had a single high affinity binding site with Kd=0.10 nM and Bmax=52.2 fmol/mg protein.
|
