Bradycardic responses to microinjection of N-methyl-D-aspartate into the nucleus tractus solitarius are inhibited by local activation of 5-HT(3) receptors.
Previous reports have described that glutamate ionotropic receptors in the nucleus tractus solitarius (NTS) are involved in the reflex control of heart rate, and that such a control can be inhibited by NTS-5-HT(3) receptor stimulation. In the present study, we examined in urethane anaesthetized rats the effects of intra-NTS microinjection of 1-(m-chlorophenyl)-biguanide (CPBG), a potent and selective 5-HT(3) receptor agonist, on the cardiovascular responses to local administration of glutamate ionotropic receptor agonists. Intra-NTS microinjection of CPBG reduced the atropine-sensitive bradycardia elicited by local microinjection of NMDA without affecting the cardiovascular responses to intra-NTS microinjections of AMPA or kainic acid. The reduction by CPBG of the NMDA-evoked cardiac response was blocked by prior intra-NTS microinjection of granisetron, a 5-HT(3) receptor antagonist, as well as bicuculline, a GABA(A) receptor antagonist. These results suggest that the stimulation of NTS 5-HT(3) receptors specifically reduces, via a GABA-dependent mechanism, the cardiac response to local NMDA administration.
Bonagamba
L G
LG
Department of Physiology, School of Medicine of Ribeirao Preto, Sao Paulo, Brazil.
Sévoz-Couche
C
C
N'Diaye
A
A
Uygun-Louvet
K
K
Callera
J
J
Machado
B H
BH
Hamon
M
M
Laguzzi
R
R
D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D001640:Bicuculline / Q000494:pharmacology; D001645:Biguanides / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D017829:Granisetron / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008845:Microinjections; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors; D011985:Receptors, Serotonin / Q000187:drug effects*; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017552:Solitary Nucleus / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D001640:Bicuculline; D001645:Biguanides; D018690:Excitatory Amino Acid Agonists; D018756:GABA Antagonists; D017829:Granisetron; D016202:N-Methylaspartate; D018092:Kainic Acid Receptors; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C065734:1-(3-chlorophenyl)biguanide