5-HT activates vagal afferent cell bodies in vivo: Role of 5-HT sub(2) and 5-HT sub(3) receptors

Occipital artery (OA) injections of 5-HT elicit pronounced reductions in heart rate and mean arterial blood pressure (MAP) in urethane-anesthetized rats by activation of vagal afferent cell bodies in the ipsilateral nodose ganglion. In contrast, internal carotid artery (ICA) and i.v. injections elicit similar cardiovascular responses by activation of peripheral vagal afferent terminals. The aim of this study was to examine the roles of 5-HT sub(3) and 5-HT sub(2) receptors in the 5-HT-induced activation of vagal afferent cell bodies and peripheral afferent terminals in urethane-anesthetized rats. OA, ICA and i.v. injections of 5-HT elicited dose-dependent reductions in heart rate and MAP that were virtually abolished after i.v. administration of the 5-HT sub(3) receptor antagonists, MDL 7222 or ICS 205-930. The responses elicited by the OA injections of 5-HT were markedly diminished after i.v. injection of the 5- HT sub(2) receptor antagonists, xylamidine or ketanserin, whereas the responses elicited by i.v. or ICA injections of 5-HT were not affected. The present findings suggest that (1) 5-HT sub(3) and 5-HT sub(2) receptor antagonists gain ready access to nodose ganglion cells upon i.v. administration, and (2) functional 5-HT sub(3) and 5-HT sub(2) receptors exist on the cell bodies of vagal afferent neurons mediating the cardiovascular responses elicited by OA injections of 5-HT. These findings also support a wealth of evidence that 5- HT sub(3) receptors exist on the peripheral terminals of vagal afferents, and although they do not discount the possibility that 5-HT sub(2) receptors exist on peripheral vagal afferent terminals, it appears that activation of these receptors does not have pronounced effects on 5-HT sub(3) receptor activity on terminals that mediate the hemodynamic responses to 5-HT.