Influence of some alpha 2-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-cholinergic component. The existence of alpha 2-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 alpha 2-receptor agonists UK 14,304, dexmedetomidine and clonidine on these alpha 2-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 insufflation 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 alpha 2-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 alpha 2-adrenoceptors.
Department of Pharmacology, Faculty of Health Sciences, Linköping University, Sweden.
L
L
Jacobsson
N
N
Grundström
R G
RG
Andersson
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D020926:Medetomidine; D011810:Quinoxalines / Q000494:pharmacology; D012132:Respiratory Muscles / Q000187:drug effects / Q000294:innervation; D012137:Respiratory System / Q000187:drug effects* / Q000294:innervation; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D011810:Quinoxalines; D000068438:Brimonidine Tartrate; D003000:Clonidine; D020926:Medetomidine