Presynaptic alpha adrenoceptor modulation of neurally mediated cholinergic excitatory and nonadrenergic noncholinergic inhibitory responses in guinea pig trachea.

Cholinergic and nonadrenergic noncholinergic (NANC) excitatory nerves in guinea pig trachea are subject to presynaptic alpha-2 adrenoceptor inhibitory control. Although the trachea is also innervated by NANC inhibitory nerves, little is known about their presynaptic regulation. The present study assessed the capacity of alpha-1 and alpha-2 adrenoceptor agonists to modulate NANC inhibitory nerves and for comparison, cholinergic excitatory nerves in guinea pig trachea. To eliminate effects of intrinsic sympathetic nerve stimulation and prostanoid production, tissues were pretreated with guanethidine, propranolol and indomethacin. The alpha-2 adrenoceptor agonist, clonidine (1 microM), induced a 12-fold rightward shift of the frequency-response curve for neurally mediated cholinergic contractions but had no effect on the concentration-response curve for exogenously administered acetylcholine. This action of clonidine was inhibited in a concentration-dependent manner by the alpha-2 adrenoceptor antagonist, yohimbine, and by the alpha-1 adrenoceptor antagonist, prazosin, NANC inhibitory responses were unaffected by clonidine (1 microM). The alpha-1 adrenoceptor agonist, phenylephrine (1 microM), failed to influence responses induced by cholinergic or NANC inhibitory nerve stimulation, acetylcholine or vasoactive intestinal peptide. Furthermore, in tissues treated with propranolol but not subjected to adrenergic neuronal blockade with guanethidine, neurally mediated cholinergic responses were not altered by yohimbine (0.3 microM) treatment. These results indicate that in guinea pig trachea: 1) cholinergic nerves are modulated by presynaptic, prazosin-sensitive inhibitory presynaptic alpha-2 adrenoceptors and 2) NANC inhibitory nerves do not possess presynaptic, modulatory alpha adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)