Influence of some α2--receptor agonists and antagonists on the excitatory non-adrenergic,non-cholinergic neurotransmission in the airways of guinea-pigs in vivo

Neural control of smooth muscle tension in the airways of guinea-pigs can be subdivided into at least four components: an excitatory cholinergic, an inhibitory noradrenergic, an excitatory non-adrenergic, non-cholinergic and an inhibitory non-adrenergic, non-cholinergíc component. The existence of α₂-adrenoceptors that modulate the excitatory non-adrenergic, non-cholinergic nerve activity has also been demonstrated. The aim of the present study was to investigate the dose-dependence of the selective α₂-receptor agonists UK 14,304, dexmedetomidine and clonidine on these α₂-adrenoceptors in the airway of guinea-pigs in vivo. Electrical stimulation of the cervical vagus nerves in anaesthetized guinea-pigs resulted in a biphasic response in insulllation pressure: an immediate increase due to excitation of cholinergic nerve fibres and a slower, longer-lasting increase due to activation of the excitatory non-adrenergic, non-cholinergic fibres to be studied. The cholinergic compound was abolished by atropine, leaving the excitatory non-adrenergic, non-cholinergic component as the sole response recorded during vagal stimulation. UK 14,304 and dexmedetomidine attenuated the response in a dose-dependent manner, whereas the effect of the partial agonist clonidine was less dose-related. UK 14,304 and dexmedetomidine reduced the insufflation pressure about 60 and 53% respectively at the highest dose. In conclusion, the neurotransmission in the excitatory non-adrenergic, non-cholinergic nerves is attenuated by selective α₂-receptors in a dose-dependent manner. The present study adds support to earlier observations that the excitatory non-adrenergic, non-cholinergic neural system in the airways of guinea-pigs is modulated by α₂-adrenoceptors.