Epinephrine enhances the sensitivity of rat vagal chemosensitive neurons: role of beta3-adrenoceptor.
This study was carried out to determine whether epinephrine alters the sensitivity of rat vagal sensory neurons. In anesthetized rats, inhalation of epinephrine aerosol (1 and 5 mg/ml, 3 min) induced an elevated baseline activity of pulmonary C fibers and enhanced their responses to lung inflation (20 cm H(2)O, 10 s) and right atrial injection of capsaicin (0.5 microg/kg). In isolated rat nodose and jugular ganglion neurons, perfusion of epinephrine (3 microM, 5 min) alone did not produce any detectable change of the intracellular Ca(2+) concentration. However, immediately after the pretreatment with epinephrine, the Ca(2+) transients evoked by chemical stimulants (capsaicin, KCl, and ATP) were markedly potentiated; for example, capsaicin (50 nM, 15 s)-evoked Ca(2+) transient was increased by 106% after epinephrine (P < 0.05; n = 11). The effect of epinephrine was mimicked by either BRL 37344 (5 microM, 5 min) or ICI 215,001 (5 microM, 5 min), two selective beta(3)-adrenoceptor agonists, and blocked by SR 59230A (5 microM, 10 min), a selective beta(3)-adrenoceptor antagonist, whereas pretreatment with phenylephrine (alpha(1)-adenoceptor agonist), guanabenz (alpha(2)-adrenoceptor agonist), dobutamine (beta(1)-adrenoceptor agonist), or salbutamol (beta(2)-adrenoceptor agonist) had no significant effect on capsaicin-evoked Ca(2+) transient. Furthermore, pretreatment with SQ 22536 (100-300 microM, 15 min), an adenylate cyclase inhibitor, and H89 (3 microM, 15 min), a PKA inhibitor, completely abolished the potentiating effect of epinephrine. Our results suggest that epinephrine enhances the excitability of rat vagal chemosensitive neurons. This sensitizing effect of epinephrine is likely mediated through the activation of beta(3)-adrenoceptor and intracellular cAMP-PKA signaling cascade.
Gu
Qihai
Q
Department of Physiology, University of Kentucky Medical Center, Lexington, Kentucky 40536-0298, USA.
Lin
You-Shuei
YS
Lee
Lu-Yuan
LY
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000008:administration & dosage*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D022702:Receptors, Adrenergic, beta-3; D004837:Epinephrine