Release of Substance P, Acetylcholine and Methionine Enkephalin from Mouse Cerebral Slices: Effects of Nicotine

Acetylcholine (ACh) is released both spontaneously and upon electrical stimulation of the nerve. Both of these processes are dependent upon the influx of extracellular Ca++ ions. Two feedback systems, one positive and the other negative, were postulated for the autoregulation of ACh release from mouse or rat cerebral slices [1-2]. The components of the positive feedback system included muscarinic receptors (Ms), Substance P (SP) and Ca++ uptake by the nerve (Figure 1). If the amount of ACh in the synaptic gap was low, a positive feedback was triggered causing the release of SP either directly or by a disinhibition phenomenon. The released SP increased the uptake of Ca++ and amplified further release of ACh. This amplification of the rate of ACh release proceeded to a certain limit when the negative feedback system was triggered. The components of this negative feedback system were muscarinic receptors (Mi), methionine enkephalin (MEK) and Ca++ uptake by the nerve. High levels of ACh triggered MEK release which depressed Ca++ uptake and the rate of ACh release from the mouse cerebral slices.