Premium
Participation of presynaptic noradrenergic fibers in the suppression of α 2 ‐adrenoceptor activity by substance P at the nucleus reticularis gigantocellularis of the rat
Author(s) -
Len WenBin,
Tsou MeiYung,
Chan Samuel H. H.,
Chan Julie Y. H.
Publication year - 1995
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890210411
Subject(s) - guanabenz , microdialysis , chemistry , norepinephrine , agonist , medicine , neurotransmission , endocrinology , extracellular , neurotransmitter , catecholamine , pentobarbital , receptor , biochemistry , dopamine
Abstract We applied reverse microdialysis and high performance liquid chroma‐ tography (HPLC) analysis to evaluate the participation of presynaptic noradrenergic neurotransmission in the suppression by substance P (SP) of a,‐adrenoceptor activity a t the nucleus reticularis gigantocellularis (NRGC) in Sprague‐Dawley rats anesthetized with pentobarbital sodium. Microinfusion of SP (600 μM/min) into the NRGC through a stereotaxically positioned microdialysis probe attenuated the hypotensive and brady cardiac actions of the α2‐adrenoceptor agonist, guanabenz (100 μgkg, i.v.). This inhibitory effect correlated positively with the time course of elevation in the estimated extracellular concentrations of SP and norepinephrine (NE) in the NRGC. Direct microinfusion of NE (50 μmin) into the NRGC also lessened the cardiosuppressant effects of guanabenz. These circulatory and NE responses to SP were, however, significantly blunted in rats in which the noradrenergic innervation in the NRGC was depleted with N‐(2‐chloroethyl)‐ N‐ethyl‐2‐bromobenzylamine hydrochloride (DSP4) pretreatment. Microinfusion of NE into the NRGC of DSP4‐pretreated animals restored the attenuation of guanabenz‐ induced cardiovascular suppression. These results suggest that SP may depress the activity of α2‐adrenoceptor a t the NRGC that are involved in circulatory regulation by increasing the extracellular concentration of NE via a presynaptic modulation of noradrenergic neurotransmission. © 1995 Wiley‐Liss, Inc.