Evidence for inhibition of sympathetic neurotransmission by endogenously released acetylcholine in the guinea‐pig trachea

Abstract

1 Interactions between pulmonary cholinergic and noradrenergic nerves were studied in the innervated tracheal tube preparation isolated from guinea-pigs anaesthetized with urethane. Relaxations of the trachealis smooth muscle in response to postganglionic stimulation of the sympathetic nerve were recorded as decreases in the intraluminal pressure of the tracheal tube after the pressure had been raised with the stable thromboxane-mimetic, U46619. In contrast, contractions following preganglionic stimulation of the vagal nerve trunk were recorded as increases in intraluminal pressure.2 In approximately half of the preparations studied, concurrent stimulation of the vagal nerve trunk inhibited relaxation responses elicited by stimulation of the sympathetic nerves. The vagi were stimulated at parameters which caused no change in intraluminal pressure, excluding the involvement of postjunctional mechanisms. 3 The effect of simultaneous stimulation of the sympathetic nerve trunk was studied on contractile responses evoked by preganglionic stimulation of the vagus nerve. In 80% of the preparations tested the vagal responses were inhibited. This inhibitory effect of sympathetic nerve stimulation was antagonized by propranolol. 4 The potassium channel agonist, cromakalim, endothelins 1 and 3 and the neuropeptides, vasoactive intestinal peptide, neurokinin A and substance P, did not significantly modulate sympathetic nerveinduced relaxations. 5 The anticholinesterase drug, physostigmine, induced a concentration-dependent increase in the intraluminal pressure of the tracheal tube and potentiated the postjunctional action of exogenously applied acetylcholine to contract the guinea-pig trachealis muscle. In the presence of higher concentrations of physostigmine both vagally-induced contractions and sympathetic nerve-induced relaxations were reduced. Atropine blocked both the inhibitory effect of physostigmine on sympathetic relaxations and its postjunctional contractile action on the trachealis smooth muscle. 6 It is concluded that, in the guinea-pig trachea, acetylcholine released endogenously from pulmonary parasympathetic nerves, either by anticholinesterase drugs or in response to nerve stimulation, can inhibit transmission in the adjacent sympathetic nerves via activation of prejunctional muscarinic heteroreceptors, probably of the M3 subtype.

Nerve growth factor expression in parasympathetic neurons: regulation by sympathetic innervation

“…In the heart, for example, vagal parasympathetic nerves attenuate myocardial contractile activity through cholinergic inhibition of norepinephrine release from sympathetic varicosities (Vanhoutte & Levy, 1980; Yang & Levy, 1992). Parasympathetic prejunctional inhibition of sympathetic axons occurs in a number of other effector organs including vas deferens (Stjärne, 1975), vascular smooth muscle (Vanhoutte et al ., 1981), trachea (Pendry & Maclagan, 1991a, b), bladder (Mattiasson et al ., 1987) and periorbital smooth muscle (Smith & Beauregard, 1993). Sympathetic nerves also act prejunctionally to inhibit parasympathetic neurotransmission (de Groat & Booth, 1980; Somogyi et al ., 1995).…”

β‐Adrenoceptors mediate inhibition of [3H]‐acetylcholine release from the isolated rat and guinea‐pig trachea: role of the airway mucosa and prostaglandins

“…Evidence for a presynaptic communication between the two branches of the autonomic nervous system has been found in functional studies. Using the innervated tube preparation of the guinea pig trachea evidence was found for presynaptic inhibition by acetylcholine or noradrenaline release from adjacent sympathetic nerves (Pendry & Maclagan, 1991). In contrast, P-adrenoceptor agonists have been found to inhibit contractions evoked by vagal stimulation more effectively than those evoked by bath-applied acetylcholine (Vermeire & Vanhoutte, 1979;Danser et al, 1987;Ito, 1988;Aizawa et al, 1991).…”

“…obtain evidence for an inhibitory action of noradrenaline (Martin & Collier, 1986). In this study, acetylcholine release was measured after blockade of cholinesterase, a condition which is known to affect presynaptic mechanisms (Kilbinger & Wessler, 1980;Pendry & Maclagan, 1991;Wessler, 1992;Wessler et al, 1992). Recently, we have reported a radiotracer method for the measurement of the release of newly synthesized [3H]-acetylcholine from the rat or guinea pig isolated trachea in the absence of cholinesterase inhibitors (Wessler et al, 1990;.…”

Endogenous noradrenaline release from guinea‐pig isolated trachea is inhibited by activation of M2 receptors

“…Jones et al, 1980) and functional (e.g. Pendry & Maclagan, 1991b) evidence that cross talk between the two neuronal systems may occur. For example, the sympathetic neurotransmission can be inhibited via presynaptic muscarinic receptors.…”