Visualization of beta-adrenoceptor binding sites on human inferior vagal ganglia and their axonal transport along the rat vagus nerve.
DESIGN: Because of uncertainties regarding the complete antihypertensive mechanism of action of beta-adrenoceptor antagonists, the present study determined whether vagal afferent neurons of humans and rats possess beta-adrenoceptors. Such a location would provide an appropriate target for beta-blockers to modulate neurotransmission of barosensitive neurons, thereby affecting blood pressure. Therefore, in vitro receptor autoradiography of high-affinity beta-adrenoceptor binding sites was performed on slices of human and rat inferior vagal (nodose) ganglia with [125I]-pindolol. METHODS: Slide-mounted sections of human and rat inferior vagal ganglia were incubated with [125I]-pindolol in the absence or presence of propranolol (10 mumol/l) to define non-specific binding, atenolol (10 mumol/l) to inhibit binding to beta 1-adrenoceptors, or ICI 118551 (3 nmol/l) to inhibit binding to beta 2-adrenoceptors. Unilateral vagal ligation was also performed in the rat to study whether beta-adrenoceptors are subject to axonal transport along the vagus nerve. RESULTS: [125I]-pindolol bound with > 90% specific binding to sections both of human and of rat inferior vagal ganglia. Specific binding occurred over both neuronal perikarya and nerve fibres. In both species the beta 2-adrenoceptor subtype appeared to predominate, as defined by the differential ability of ICI 118551 (beta 2) and atenolol (beta 1) to inhibit the binding of [125I]-pindolol. Furthermore, unilateral vagal ligation in the rat caused an accumulation of specific binding adjacent to the ligature sites. CONCLUSIONS: We conclude that human and rat vagal afferent (and efferent) neurons possess beta-adrenoceptors that potentially could explain the mechanism of action of beta-adrenoceptor antagonists in the therapy of hypertension.[1]References
- Visualization of beta-adrenoceptor binding sites on human inferior vagal ganglia and their axonal transport along the rat vagus nerve. Lawrence, A.J., Watkins, D., Jarrott, B. J. Hypertens. (1995) [Pubmed]
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