POSSIBLE MECHANISMS OF THE EFFECT OF PHYSOSTIGMINE ON THE FACILITATION OF ACETYLCHOLINE-RELEASE IN THE GUINEA-PIG MYENTERIC PLEXUS

The automodulation of acetylcholine (ACh) release in the guinea pig my enteric plexus-longitudinal muscle preparation was investigated by stu dying the electric stimulation-evoked release of radiolabeled ACh. Whe n the release associated with neuronal activity was challenged by the muscarinic antagonist atropine, the release was not significantly enha nced. When the acetylcholinesterase (AChE) blocker physostigmine was p resent, the well-established muscarinic receptor-mediated autoinhibiti on was operative, i.e., the release was significantly reduced. However , when both drugs were added together, the release was much higher tha n under control conditions. Therefore, it seems likely that there is a lso a facilitatory system. We made an effort to clear up the mechanism of this facilitation by blocking possible nicotinic presynaptic recep tors, by excluding the alpha(2)-adrenoceptor-mediated masking effect o f noradrenergic heteromodulation, by preventing a possible ATP-mediate d mechanism, and by attempting to prevent the direct effect of physost igmine. None of these manipulations resulted in a decrease of the surp lus release. It is concluded, that when the negative feedback modulati on of ACh is inhibited and AChE activity is reduced, high levels of AC h facilitates additional release of ACh from the nerve terminals, poss ibly through a not yet verified class of receptors.