Central neuropeptides play important roles in many instances of physiological and pathophysiological regulation mediated through the autonomic nervous system. In regard to the hepatobiliary system, several neuropeptides act in the brain to regulate bile secretion, hepatic blood flow, and hepatic proliferation. Stressors and sympathetic nerve activation are reported to exacerbate experimental liver injury. Some stressors are known to stimulate corticotropin-releasing factor (CRF) synthesis in the central nervous system and induce activation of sympathetic nerves in animal models. The effect of intracisternal CRF on carbon tetrachloride (CCl₄)-induced acute liver injury was examined in rats. Intracisternal injection of CRF dose dependently enhanced elevation of the serum alanine aminotransferase (ALT) level induced by CCl₄. Elevations of serum aspartate aminotransferase, alkaline phosphatase, and total bilirubin levels by CCl₄ were also enhanced by intracisternal CRF injection. Intracisternal injection of CRF also aggravated CCl₄-induced hepatic histological changes. Intracisternal CRF injection alone did not modify the serum ALT level. Intravenous administration of CRF did not influence CCl₄-induced acute liver injury. The aggravating effect of central CRF on CCl₄-induced acute liver injury was abolished by denervation of hepatic plexus with phenol and by denervation of noradrenergic fibers with 6-hydroxydopamine treatment but not by hepatic branch vagotomy or atropine treatment. These results suggest that CRF acts in the brain to exacerbate acute liver injury through the sympathetic-noradrenergic pathways.

sympathetic nerve; noradrenergic nerve; peptide; hepatic damage; central nervous system

This article has been cited by other articles:

				D. W. Adelson, H. P. Kosoyan, Y. Wang, J. Z. Steinberg, and Y. Tache Gastric Vagal Efferent Inhibition Evoked by Intravenous CRF Is Unrelated to Simultaneously Recorded Vagal Afferent Activity in Urethane-Anesthetized Rats J Neurophysiol, April 1, 2007; 97(4): 3004 - 3014. [Abstract] [Full Text] [PDF]

				H.-J. Yu, B.-R. Lin, H.-S. Lee, C.-T. Shun, C.-C. Yang, T.-Y. Lai, C.-T. Chien, and S.-M. Hsu Sympathetic vesicovascular reflex induced by acute urinary retention evokes proinflammatory and proapoptotic injury in rat liver Am J Physiol Renal Physiol, May 1, 2005; 288(5): F1005 - F1014. [Abstract] [Full Text] [PDF]

				Y. Nakade, D. Tsuchida, H. Fukuda, M. Iwa, T. N. Pappas, and T. Takahashi Restraint stress delays solid gastric emptying via a central CRF and peripheral sympathetic neuron in rats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2005; 288(2): R427 - R432. [Abstract] [Full Text] [PDF]

				Y. Nakade, M. Yoneda, K. Nakamura, I. Makino, and A. Terano Involvement of endogenous CRF in carbon tetrachloride-induced acute liver injury in rats Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2002; 282(6): R1782 - R1788. [Abstract] [Full Text] [PDF]