Vol. 277, Issue 5, H1914-H1923, November 1999
5-HT4 receptors in nucleus
tractus solitarii attenuate cardiopulmonary reflex in anesthetized
rats
Emma
Edwards and
Julian F. R.
Paton
Department of Physiology, School of Medical Sciences, University
of Bristol, Bristol BS8 1TD, United Kingdom
We determined whether the cAMP-protein kinase
A (PKA) pathway modulation of the cardiopulmonary reflex was caused by
activation of 5-HT4 receptors at
the level of the nucleus tractus solitarii (NTS) of the anesthetized
rat. NTS microinjection of 5-methoxytryptamine (5-MeOT, 2.25 pmol,
n = 13), a 5-HT-receptor agonist,
attenuated the cardiopulmonary reflex-evoked bradycardia and tachypnea.
Microinjection of RS-39604 (4.5 pmol,
n = 6), a selective
5-HT4-receptor antagonist, blocked
the attenuating effect of 5-MeOT. NTS microinjection of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP, 9 nmol, 45 nl, n = 10), a membrane-permeant analog
of cAMP, significantly attenuated the reflex bradycardia and tachypnea.
Rp-adenosine 3',5'-cyclic monophosphorothioate (4.5 nmol,
n = 6), a cAMP-dependent PKA
inhibitor, had no effect on the cardiopulmonary reflex when microinjected into the NTS alone but when given before a microinjection of either 8-BrcAMP (n = 6) or 5-MeOT
(n = 6) blocked the attenuating effect
on the reflex-evoked bradycardia. Thus stimulation of
5-HT4 receptors within the NTS
depresses the reflex bradycardia components of the cardiopulmonary
reflex via a cAMP-dependent PKA pathway.
8-bromoadenosine 3',5'-cyclic monophosphate; protein
kinase A; 5-methoxytryptamine; phenyl biguanide
