Pharmacological modulation of cholinergic neurotransmission in guinea pig trachea in vitro

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 attenuat...