Role of serotonin3 receptors in the nucleus tractus solitarius in
the carotid chemoreflex.
S[acute]evoz, Caroline, Joao-Carlos Callera, Benedito H. Machado,
Michel Hamon, and Raul Laguzzi.
INSERM U.288, C. H. U. Piti[acute]e-Salp[circumflex]etri[grave]ere,
75634 Paris Cedex 13, France, and Department of Physiology, School of
Medicine of Ribeirao Preto, U. S. P., 14049-900, Ribeirao Preto, Sao
Paulo, Brazil
APStracts 3:0509H, 1996.
The effects of serotonin3 (5-HT3) receptor stimulation in the nucleus
tractus solitarius (NTS) upon the cardiovagal, sympathetic and
respiratory responses to activation of carotid body chemoreceptors
were investigated in anaesthetized rats. The chemoreflex responses
were triggered by an intravenous administration of KCN (40 [mu]g/kg)
in spontaneously breathing urethane-chloralose-anaesthetized rats or
by an intra-carotid administration of saline saturated with 100% CO2
in pancuronium-paralyzed and artificially ventilated urethane
-anaesthetized rats. Microinjections of 5-HT (2.5-5 nmol) or of the 5
-HT3 agonist 1-(m-chlorophenyl)-biguanide (CPBG, 300-1200 pmol) into
the commissural NTS blocked, in a dose dependent manner, the
atropine-sensitive chemoreflex bradycardia elicited by KCN. However,
neither 5-HT nor CPBG affected the KCN-induced increase in
respiratory volume and the CO2-induced increases in blood pressure
and lumbar sympathetic nerve discharge. The inhibitory effect of 5-HT
or CPBG upon KCN-induced bradycardia was blocked by prior intra-NTS
microinjection of a 5-HT3 antagonist, such as zacopride (100 pmol) or
ondansetron (100 pmol), or the GABAA antagonist, bicuculline (10
pmol). In contrast, local microinjections of antagonists acting at 5
-HT1 and 5-HT2 receptors, such as methysergide (100 pmol) and
ketanserin (10 pmol), respectively, did not prevent the actions of 5
-HT or CPBG. These data show that the stimulation of 5-HT3 receptors
in the NTS exerted, probably through the activation of a local
GABAergic system, an inhibitory influence on the cardiovagal
component of the chemoreflex. Since similar effects of 5-HT3 receptor
stimulation in the NTS were previously found on the baroreflex- and
the Bezold-Jarisch- reflex responses, it can be inferred that NTS 5
-HT3 receptors play a key modulatory role in the reflex control of the
heart rate.
Received 14 March 1996; accepted in final form 24 September 1996.
APS Manuscript Number H247-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996