Holzer P, Wachter C, Heinemann A, Jocic M, Lippe I T, Herbert M K
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
Arch Int Pharmacodyn Ther. 1995 Jan-Feb;329(1):67-79.
Primary afferent neurons, originating from the dorsal root ganglia, provide a perivascular network of fibres around the arterial system throughout the body. When stimulated, these fibres cause a nonadrenergic noncholinergic (NANC) vasodilatation by release of calcitonin gene-related peptide (CGRP). This peptide is a potent vasodilator and, in this action, cooperates with nitric oxide (NO) in a tissue-specific manner. The hyperaemic effect of intravascularly injected rat CGRP-alpha in the rat gastric mucosa is reduced by blockade of the NO synthesis, which indicates that CGRP dilates the gastric microvascular bed via NO-dependent and -independent mechanisms. This is also true for endogenous CGRP, as the gastric mucosal hyperaemia, which is caused by gastric acid challenge and involves CGRP, is likewise blocked by inhibition of the NO synthesis. The CGRP/NO-mediated vasodilatation is an important element of a neural emergency system that strengthens the resistance of the gastric mucosa in the face of pending acid injury. In the rat skin, CGRP participates in neurogenic inflammatory processes but the cutaneous vasodilator action of exogenous CGRP and the CGRP-mediated vasodilatation, evoked by antidromic stimulation of afferent nerve fibres, do not depend on the formation of NO. This L-arginine-derived autacoid, however, plays a role in the release of CGRP from afferent nerve fibres in the skin since it contributes to the CGRP-mediated vasodilator responses to chemical irritation or immunological challenge via interleukin-1 beta. These data indicate that the type of interaction between CGRP and NO in causing a NANC vasodilatation varies with the vascular bed under study. Depending on the tissue, NO may facilitate the release of CGRP from afferent nerve fibres or be a secondary vasorelaxant messenger of the peptide.
初级传入神经元起源于背根神经节，在全身动脉系统周围形成一个血管周围纤维网络。受到刺激时，这些纤维通过释放降钙素基因相关肽（CGRP）引起非肾上腺素能非胆碱能（NANC）血管舒张。这种肽是一种强效血管舒张剂，在这一作用中，它以组织特异性方式与一氧化氮（NO）协同作用。血管内注射大鼠CGRP-α在大鼠胃黏膜中产生的充血效应，会因NO合成受阻而减弱，这表明CGRP通过依赖NO和不依赖NO的机制使胃微血管床舒张。内源性CGRP也是如此，因为胃酸刺激引起的、涉及CGRP的胃黏膜充血，同样会因NO合成受到抑制而被阻断。CGRP/NO介导的血管舒张是神经应急系统的一个重要组成部分，在面临即将发生的酸损伤时，可增强胃黏膜的抵抗力。在大鼠皮肤中，CGRP参与神经源性炎症过程，但外源性CGRP的皮肤血管舒张作用以及传入神经纤维的逆行刺激所诱发的CGRP介导的血管舒张并不依赖NO的形成。然而，这种由L-精氨酸衍生的自分泌物质在皮肤传入神经纤维释放CGRP的过程中发挥作用，因为它通过白细胞介素-1β促进CGRP介导的对化学刺激或免疫挑战的血管舒张反应。这些数据表明，CGRP和NO在引起NANC血管舒张时的相互作用类型因所研究的血管床而异。根据组织的不同，NO可能促进CGRP从传入神经纤维中释放，或者是该肽的继发性血管舒张信使。
