Prolonged stimulation of respiration by brainstem metabotropic
glutamate receptors.
Li, Aihua, and Eugene E. Nattie.
Department of Physiology, Dartmouth Medical School, Lebanon, N.H.
03756-0001
APStracts 2:0290A, 1995.
Stimulation of metabotropic glutamate receptors (mGluRs) in the
retrotrapezoid nucleus (RTN) of chloralose-urethane anesthetized rats
by the mGluR agonist (1S,3R)- aminocyclopentanedicarboxylic acid
(ACPD, 10 nl, 1 mM) increases integrated phrenic amplitude (PNA) for
> 60 min. Here we ask if the mGluR antagonist (+/-)-[mu]-methyl
-4- carboxyphenylglycine [(+/-)-MCPG] can block this effect . Using
multi-barreled micropipettes, we first identified RTN sites that
affect respiration by noting short-lived stimulation of PNA produced
by brief duration injection of glutamate (10 nl, 100 mM), a presumed
ionotropic receptor response. We then injected the active or inactive
isomer of (+/-)-MCPG (10 nl, 10 mM) followed by ACPD or by a long
duration (60 sec) injection of glutamate (10 nl, 100 mM) at the same
site. Each injection location was verified anatomically. The active
antagonist (+/-)-MCPG itself had no significant effect on PNA but it
blocked a) subsequent (1S, 3R) ACPD-induced PNA stimulation for 99
+/-11 min (mean +/- SEM) and b) the PNA response to 60 sec glutamate
injection for 66 +/-6 min. The inactive form (-)-MCPG had no effect
on (1S,3R) ACPD induced PNA stimulation. We conclude; 1) RTN mGluRs
may be involved in respiratory control, 2) they are not active in
eupnea, and 3) their stimulation may require prolonged glutamate
release.
Received 6 April 1995; accepted in final form 12 June 1995.
APS Manuscript Number A377-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 11 July 1995.