Document Detail


Catestatin has an unexpected effect on the intrathecal actions of PACAP, dramatically reducing blood pressure.
MedLine Citation:
PMID:  22874427     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
This study focuses on presympathetic neurons of the rostral ventrolateral medulla (RVLM) that regulate sympathetic vasomotor tone. Many neurotransmitters are co-localized in RVLM neurons and are released under specific conditions to modulate efferent homeostatic responses. Of particular interest here, are two peptides co-localized in catecholaminergic RVLM neurons: catestatin, and pituitary adenylate cyclase-activating polypeptide (PACAP). Chromogranin A derived catestatin, is a potent endogenous non-competitive nicotinic and adrenoreceptor antagonist. Catestatin impairs adenylate cyclase and phospholipase C action; mechanisms engaged by PACAP. Although PACAP and catestatin are likely co-released, the possible effects of this are unknown. We aimed to determine if catestatin affects the normal sympathoexcitatory but isotensive responses to intrathecal PACAP. Urethane-anesthetized, vagotomized, ventilated Sprague-Dawley rats (n = 22) were given an intrathecal injection of catestatin at different times prior to intrathecal administration of PACAP-38. Arterial pressure, splanchnic sympathetic nerve activity, heart rate and reflex responses to baroreceptor and chemoreceptor activation were recorded. The key findings of this study are that pre-treatment with catestatin time-dependently enhances the PACAP-38 effect on mean arterial pressure, and enhances sympathetic barosensitivity and chemosensitivity. The time-scale of the effect of catestatin on the response to PACAP-38 strongly suggests that catestatin is either causing changes in gene expression to exert its effects, or modifying intracellular mechanisms normally engaged by PAC1 receptors. The ability of catestatin pre-treatment to enhance barosensitivity and chemosensitivity after PACAP-38 injection, supports the hypothesis that catestatin manipulates the intracellular environment within sympathetic nerves in a way that increases responses to PACAP.
Authors:
Andrea H Gaede; Melissa A Inglott; Melissa Mary-Jean Farnham; Paul M Pilowsky
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-8
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  -     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Macquarie University.
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