Pharmacological modulation of cholinergic neurotransmission in guinea pig trachea in vitro

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Abstract
Electrical (field) stimulation of the isolated guinea pig trachea with normal intrinsic tone produced a biphasic response which consisted of an initial (cholinergic) contraction followed by (adrenergic and nonadrenergic) relaxation. Treatment of the tissue with the prostaglandin synthetase inhibitor indomethacin (2.8–5.6 μM) removed intrinsic tone and increased the responsiveness of the tissue to stimulation of cholinergic nerves and to exogenous acetylcholine. Indomethacin-relaxed tracheae were subsequently used to study cholinergic neurotransmission because under these experimental conditions only the contractile component of the response to electrical stimulation was observed. The β adrenoceptor blocking agents dl-propranolol and sotalol and the adrenergic neuron blocking agent guanethidine produced further enhancement of the contraction to electrical stimulation at low frequency (1–10 Hz). Prostaglandin E1, l-noradrenaline, l-adrenaline, salbutamol, phenylephrine, and phentolamine selectively attenuated the contractions to electrical stimulation in concentrations which did not significantly alter the matched responses to exogenous acetylcholine. The selective depressant effect of l-noradrenaline, l-adrenaline, salbutamol, phenylephrine, and phentolamine but not prostaglandin E1 were blocked by dl-propranolol or sotalol. The present results demonstrate that responses to stimulation of cholinergic nerves were altered by (1) prostaglandins and inhibitors of their synthesis, (2) neurally released adrenergic transmitter, and (3) exogenously added β adrenoceptor agonists. The possibility that prostaglandins and adrenergic neurotransmitter may modulate cholinergic neurotransmission at both pre- and post-junctional sites is hypothesized. It is proposed that more attention should be paid to the role of cholinergic transmission and its modulation in the studies of airway smooth muscle.