Facilitatory and inhibitory muscarine receptors on the rat phrenic nerve: effects of pirenzepine and dicyclomine.

Neuronal transmitter stores of the rat phrenic nerve were labelled by an incubation with [3H]choline. Release of [3H]acetylcholine was elicited either by a short (100 pulses, 5 Hz) or by a long (1500 pulses, 5 or 25 Hz) period of electrical nerve stimulation. Pirenzepine and dicyclomine enhanced transmitter release evoked by the short stimulation period. Both antagonists reduced transmitter release evoked by the long stimulation period. Pirenzepine reduced transmitter release at low concentrations (1 nmol/l) whereas a higher concentration was necessary for the enhancing effect; the opposite pattern was found for dicyclomine. A low concentration of oxotremorine (10 nmol/l) enhanced and a high concentration (1 mumol/l) reduced transmitter release evoked by the short stimulation period. Both effects could be prevented by a low concentration of pirenzepine (10 nmol/l). It is concluded that facilitatory and inhibitory muscarine receptors are present on the motor nerve. A short stimulation period activates predominantly the negative muscarinic feedback, whereas during a long period of continuous nerve stimulation the positive muscarinic feedback mechanism is additionally activated. Both the facilitatory and inhibitory receptors might be regarded as M1-receptors but differences in the pharmacological properties between both receptor populations appear possible.