| Budget Amount *help |
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1987: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1986: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Research Abstract |
In isolated right and left atria of the guinea-pig, the presence of cardioacceleratory nonadre-nergic noncholinergic nerves was found, in addition to the classical sympathetic adrenergic and parasympathetic cholinergic nerves (1). For this study, an unique method was utilized, which we newly developed for the transmural nerve stimulation of the cardiac tissues in vitro (1). It has also been elucidated that the neurotransmitter of the nonadrenergic noncholinergic nerve was CGRP, calcitonin gene-related peptide. CGRP exerted not only cardioacceleratory actions but also vasodilator actions on a variety of arterial smooth muscles. In the study with spiral strips of the porcine coronary artery, CGRP was revealed to be one of the most potent vasodilators known (2). The mechanisms of action of CGRP were also investigated, and it has been demonstrated that CGRP produces both cardioacceleration and vasodilation by ultimately elevating the tissue levels of cyclic AMP via increasing adenylate cyc
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lase activity (2,3). CGRP-binding proteins were solubilized and characterized, the molecular sizes of which were 70 kD and 120 kD in the cardiac muscle and 70 kD and 90 kD in the coronary artery of the pig (4). The proteins exhibited no interaction with other endogenous peptides including calcitonin, indicating that they are specific receptors for CGRP. It can be speculated, therefore, that CGRP may act by stimulating its specific receptors and then, presumably via interaction with GTP-binding protein, activate adenylate cyclase. In the perfused mesenteric vascular bed of the rat, the existence of potent nonadrenergic noncholinergic vasodilator nerves has been demonstrated. Interestingly, the neurotransmitter of the vasodilator nerves was also CGRP (5). This is the first case to clearly show the presence of vasodilator nerves in the peripheral vascular tissuse. Taken together, the local blood flow of various peripheral tissues, e.g. cardiac tissues, mesenteric vasculature, etc. is coceivable to be regulated by novel vasodilator nerves as well as classical autonomic nerves.
Recently, we isolated and purified a potent vasoconstrictor peptide, endothelin, from the culture medium of the porcine endothelial cells. The structure and pharmacological characteristics of endothelin are extremely different from those of currently known endogenous peptides. The phy-siological functions and drug sensitivity of cardiovascular tissues now appear to be under the control of complex nervous, humoral and endotherial systems. Less
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