Key result
Stimulation of 5-HT4 receptors within the NTS using 5-MeOT or 8-BrcAMP attenuated cardiopulmonary reflex-evoked bradycardia via a cAMP-dependent PKA pathway.
This preclinical study demonstrates that 5-HT4 receptor activation in the nucleus tractus solitarii attenuates cardiopulmonary reflex bradycardia via the cAMP-PKA pathway.
No immediate clinical implications; extends preclinical mapping of NTS 5-HT4 signaling but leaves open human translation.
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.
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Edwards et al. (1999) studied Cardiopulmonary reflex in anesthetized rats. NTS microinjection of 5-methoxytryptamine (5-MeOT) or 8-BrcAMP vs. RS-39604 (5-HT4 antagonist) or Rp-cAMPS (PKA inhibitor) was evaluated on Cardiopulmonary reflex-evoked bradycardia and tachypnea. Stimulation of 5-HT4 receptors within the NTS using 5-MeOT or 8-BrcAMP attenuated cardiopulmonary reflex-evoked bradycardia via a cAMP-dependent PKA pathway.
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