Effects of atropine and glycopyrrolate on neuromuscular transmission in the rat phrenic nerve-diaphragm preparation

1. 1. The effects of atropine and glycopyrrolate on neuromuscular transmission and on muscle contraction, were studied, in the rat diaphragm preparation, by analyzing their effects on the indirectly (and directly)-elicited twitch (0.2 Hz), tetanic (50 Hz for 20 sec duration), post-tetanic twitch responses (at 5 sec after the tetanus), and on the phenomenon of post-tetanic twitch potentiation (PTP), which is thought to be of a presynaptic origin, i.e. due to increased transmitter release. 2. 2. Atropine (0.001–10 μM) increased the indirectly-elicited twitch tension by 22 ± 2.1% (control 0.9 ± 0.1 g, P < 0.02), the tetanus by 15 ± 1.1% (control 3.9 ± 0.7 g, P < 0.05), the post-tetanic twitch response by 33 ± 3.1% (control 1.2 ± 0.1 g, P < 0.01) and the PTP value by 36 ± 1.9% (control 33 ± 2.3%, P < 0.01, means ± SEM = 6). 3. 3. Atropine (0.001–10 μM) had little effect on the directly-elicited twitch tension, but in high concentrations (e.g. 20 μM), it blocked the twitch tension. 4. 4. In contrast, glycopyrrolate (0.1–100 μM) had little effect on the twitch tension (direct or indirect), but it significantly reduced the tetanus (by 38 ± 3.5%, P < 0.01), the post-tetanic twitch response (by 17 ± 1.2%, P < 0.05) and the PTP values (by 24 ± 3.1% P < 0.02). 5. 5. In the presence of hemicholinium (1.3 μM) the responses to atropine and glycopyrrolate were altered (decreased), indicating a possible action on presynaptic mechanism of transmission. 6. 6. It is concluded that atropine and glycopyrrolate produce different (opposite) effects at the rat neuromuscular junction, atropine enhances whereas glycopyrrolate depresses neuromuscular transmission. The effects of these two antimuscarinic drugs may be exerted at the presynaptic nerve terminals, i.e. on presynaptic muscarinic receptors, which are involved in the feedback mechanism of transmitter release.