Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, 1994: NEUROTRANSMITTER MECHANISMS OF RAT VAGAL AFFERENT NEURONS

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Abstract
1. The present study has employed anatomical and neurochemical techniques to assess whether the amino acid, L-glutamate, may be considered as a potential neurotransmitter at rat vagal afferent neurons, with particular reference to baroreceptor afferents. 2. Slide-mounted sections of rat nodose ganglia were incubated with a high-titre antibody to glutamate, and visualization of the resulting immunoreactivity indicated glutamate-positive staining in a population of vagal afferent perikarya. In contrast, interstitial cells were devoid of immunostaining. 3. Release of endogenous glutamate was measured by in vivo microdialysis in the nucleus tractus solitarius, the site of central vagal afferent terminals, and could be evoked with a depolarizing stimulus of KCl in a calcium-dependent fashion. In addition, baroreceptor loading with an intravenous infusion of phenylephrine (30 micrograms/kg per min) increased the spontaneous efflux of glutamate to 148 +/- 28% of basal levels, which was paralleled by an increase in mean arterial pressure (approximately 40 mmHg). Release of glutamate was also elevated two-fold by intracerebral administration of S-nitroso-N-acetylpenicillamine (30 mumol/L), an effect that could be prevented by coadministration of methylene blue (10 mumol/L). 4. These data suggest that neuronal glutamate may be formed in a population of vagal afferent cell bodies, presumably to act on soma membrane receptors. Furthermore, the excitatory amino acid is released in a neurotransmitter-like fashion at the terminal region of vagal afferent neurons, where glutamate release is increased as a consequence of baroreceptor loading and also following activation of soluble guanylate cyclase. Thus, glutamate may be considered a candidate neurotransmitter of vagal baroreceptor afferent neurons, which may be modulated by nitric oxide or an endogenous nitrosothiol.