Modulation of enteric cholinergic neurons by hetero- and autoreceptors: Cooperation among inhibitory inputs

In the guinea-pig colon, acetylcholine (ACh) release from intrinsic choline rgic motor neurons is inhibited by adrenoceptors, opioid and muscarinic rec eptors. Chronic sympathetic denervation resulted in supersensitivity to the inhibitory effect of DAMGO (mu-opioid agonist) on ACh release and on the p eristaltic reflex. After chronic treatment with naltrexone (NTX) supersensi tivity to DAMGO and subsensitivity to UK14,304 (alpha(2)-adrenoceptor agoni st) developed for both functional parameters. The facilitatory effect of sc opolamine on ACh release remained unchanged after chronic NTX treatment, wh ereas it was potentiated after chronic sympathetic denervation. These data suggest the existence of a functional interaction between different inhibit ory pathways modulating cholinergic motor neurons in the guinea-pig colon. Namely, chronic manipulation of an inhibitory pathway may entail adaptive s ensitivity changes in another inhibitory pathway so that homeostasis can be maintained.