| Research Abstract |
1. Central Cardiovascular Regulation of Tachykinin Peptides
The central pressor responses to the tachykinin peptides were dose-dependent, reaching maxima 4-6 min after injections of the peptides and then persisting for at least 40 min. The pressor responses due to substance P (SP), neurokinin A (NKA) and neuropeptide gamma (NPgamma) were blocked by sympathetic blocking agents. In contrast, the pressor response to an neurokinin B (NKB) analogue senktide was not blocked by the ganglionic blocking agent or adrenalectomy. The senktide-induced pressor response was inhibited by pretreatment with a vasopressin antagonist, and senktide caused an increase in plasma vasopressin level. However, the vasopressin antagonist did not influence the SP-, NKA- and NPgamma-induced pressor responses.
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, whereas central NKB, derived from
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the preprotachykinin B gene, increase the BP via release of vasopressin from the hypothalamus
2. Pharmacological properties of the tachykinin receptor subtype in the endothelial cell and vasodilation.
Vascular endothelial cells are involved in the regulation of vascular tone through production of an endothelium-derived relaxing factor (EDRF). SP and related peptides have shown to cause endotheliumdependent relaxation of precontracted arteries of several mammalian species. 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 EDRF.
In addition, we examined ^<125>I-Bolton-Hunter 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. GTP analog caused a marked reduction in the number of the binding sites. NK-1 receptor agonists were most potent for displacing of ^<125>I-BHSP binding. This result is in agreement with the results of the vasodilating responses. Less
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