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J Appl Physiol 94: 1999-2009, 2003. First published January 3, 2003; doi:10.1152/japplphysiol.01066.2002
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Vol. 94, Issue 5, 1999-2009, May 2003

Catecholaminergic microcircuitry controlling the output of airway-related vagal preganglionic neurons

Musa A. Haxhiu1,2,3, Prabha Kc1, Burim Neziri2, Bryan K. Yamamoto4, Donald G. Ferguson3, and V. John Massari5

Departments of 1 Physiology and Biophysics and 5 Pharmacology, Howard University College of Medicine, Washington, DC 20059; and Departments of 2 Pediatrics, 3 Anatomy, and 4 Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106

In this study, we have investigated the ultrastructure and function of the catecholaminergic circuitry modulating the output of airway-related vagal preganglionic neurons (AVPNs) in ferrets. Immunoelectron microscopy was employed to characterize the nature of catecholaminergic innervation of AVPN at the ultrastructural level. In addition, immunofluorescence was used to examine the expression of the alpha 2A-adrenergic receptor (alpha 2A-AR) on AVPNs, and norepinephrine release within the rostral nucleus ambiguous (rNA) was measured by using microdialysis. Physiological experiments were performed to determine the effects of stimulation of the noradrenergic locus coeruleus (LC) cell group on airway smooth muscle tone. The results showed that 1) catecholaminergic nerve endings terminate in the vicinity of identified AVPNs but very rarely form axosomatic or axodendritic synapses with the AVPNs that innervate the extrathoracic trachea; 2) AVPNs express the alpha 2A-AR; 3) LC stimulation-induced norepinephrine release within the rNA region was associated with airway smooth muscle relaxation; and 4) blockade of alpha 2A-AR on AVPNs diminished the inhibitory effects of LC stimulation on airway smooth muscle tone. It is concluded that a noradrenergic circuit originating within the LC is involved in the regulation of AVPN activity within the rNA, and stimulation of the LC dilates the airways by the release of norepinephrine and activation of alpha 2A-AR expressed by AVPNs, mainly via volume transmission.

synaptic transmission; volume transmission; locus coeruleus; nucleus ambiguus; alpha 2A-adrenergic receptors


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