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A novel potent vasoconstrictor peptide produced by vascular endothelial cells   总被引:521,自引:0,他引:521  
An endothelium-derived 21-residue vasoconstrictor peptide, endothelin, has been isolated, and shown to be one of the most potent vasoconstrictors known. Cloning and sequencing of preproendothelin complementary DNA shows that mature endothelin is generated through an unusual proteolytic processing, and regional homologies to a group of neurotoxins suggest that endothelin is an endogenous modulator of voltage-dependent ion channels. Expression of the endothelin gene is regulated by several vasoactive agents, indicating the existence of a novel cardiovascular control system.  相似文献
2.
T Sakurai  M Yanagisawa  Y Takuwa  H Miyazaki  S Kimura  K Goto  T Masaki 《Nature》1990,348(6303):732-735
Endothelin-1 was initially identified as a 21-residue potent vasoconstrictor peptide produced by vascular endothelial cells, but was subsequently found to have many effects on both vascular and non-vascular tissues. The discovery of three isopeptides of the endothelin family, ET-1, ET-2 and ET-3, each possessing a diverse set of pharmacological activities of different potency, suggested the existence of several different endothelin receptor subtypes. Endothelins may elicit biological responses by various signal-transduction mechanisms, including the G protein-coupled activation of phospholipase C and the activation of voltage-dependent Ca2+ channels. Thus, different subtypes of the endothelin receptor may use different signal-transduction mechanisms. Here we report the cloning of a complementary DNA encoding one subtype belonging to the superfamily of G protein-coupled receptors. COS-7 cells transfected with the cDNA express specific and high-affinity binding sites for endothelins, responding to binding by the production of inositol phosphates and a transient increase in the concentration of intracellular free Ca2+. The three endothelin isopeptides are roughly equipotent in displacing 125I-labelled ET-1 binding and causing Ca2+ mobilization. A messenger RNA corresponding to the cDNA is detected in many rat tissues including the brain, kidney and lung but not in vascular smooth muscle cells. These results indicate that this cDNA encodes a 'nonselective' subtype of the receptor which is different from the vascular smooth muscle receptor.  相似文献
3.
H Kawasaki  K Takasaki  A Saito  K Goto 《Nature》1988,335(6186):164-167
Systemic blood pressure is controlled by changes in the resistance of the peripheral vascular bed for example in the mesenteric blood vessels. The tone of peripheral blood vessels is primarily maintained by sympathetic vasoconstrictor nerves. Although vasodilator innervation has been identified in certain isolated elastic arteries, it is not known whether vasodilator nerves contribute to the regulation of the peripheral resistance vessels. We present pharmacological evidence for the existence of nonadrenergic, noncholinergic (NANC) vasodilator nerves in the mesenteric resistance vessel of the rat and that the resistance is controlled by not only sympathetic vasoconstrictor nerves but also NANC vasodilator nerves. We also show that the neurogenic vasodilation was selectively abolished by depleting endogenous calcitonin gene-related peptide (CGRP), a potent vasodilator neuropeptide, from perivascular nerves. This indicates that CGRP is a novel vasodilator neurotransmitter and may play a role in control of the total peripheral resistance of systemic circulation through a local reflex mechanism.  相似文献
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