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1 Physiology and Biophysics, Howard University, Washington, DC, USA; Pediatrics, Case Western Reserve University, Cleveland, OH, USA; Anatomy, Case Western Reserve University, Cleveland, OH, USA
2 Physiology and Biophysics, Howard University, Washington, DC, USA
3 Pediatrics, Case Western Reserve University, Cleveland, OH, USA
4 Psychiatry, Case Western Reserve University, Cleveland, OH, USA
5 Anatomy, Case Western Reserve University, Cleveland, OH, USA
6 Pharmacology, Howard University, Washington, DC, USA
* To whom correspondence should be addressed. E-mail: mah10{at}po.cwru.edu.
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 
-2A adrenergic receptor (-2AAR) on AVPNs, and noradrenaline release within the rostral nucleus ambiguous (rNA) was measured 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 axo-somatic or axodendritic synapses with the AVPNs that innervate the extrathoracic trachea; 2) AVPNs express the -2AAR; 3) LC stimulation-induced noradrenaline release within the rNA region was associated with airway smooth muscle relaxation; and 4) blockade of -2AAR 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 noradrenaline and activation of -2AAR expressed by AVPNs, mainly via volume transmission.
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