5-HT(4) receptors in nucleus tractus solitarii attenuate cardiopulmonary reflex in anesthetized rats.
We determined whether the cAMP-protein kinase A (PKA) pathway modulation of the cardiopulmonary reflex was caused by activation of 5-HT(4) 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-HT(4)-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-HT(4) receptors within the NTS depresses the reflex bradycardia components of the cardiopulmonary reflex via a cAMP-dependent PKA pathway.
Edwards
E
E
Department of Physiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom.
Paton
J F
JF
D008735:5-Methoxytryptamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D008168:Lung / Q000502:physiology*; D008297:Male; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D044422:Receptors, Serotonin, 5-HT4; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D044422:Receptors, Serotonin, 5-HT4; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D008735:5-Methoxytryptamine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases