Serotonergic neurotransmission in the gut

Serotonin (5-hydroxytryptamine; 5-HT) was first suggested to be a neurotransmitter in the enteric nervous system (ENS) by Gershon, Drakontides, and Ross in 1965 (38); however, it has not been until recently that 5-HT has finally satisfied all of the criteria necessary for proof of its transmitter role. 5-HT has not been shown by biochemical, histochemical, and immunocytochemical techniques to be present in enteric neurons. The amine has also been demonstrated to be released from stimulated enteric neurons by a Ca+2-dependent mechanism. The enteric neurons that contain 5-HT synthesize the amine from the dietary amino acid L-tryptophan. A specific, high-affinity uptake mechanism for 5-HT is another feature of enteric serotonergic neurons and probably serves as an inactivating mechanism for the amine. Physiologically, evidence derived by Wood and Mayer (103) from studies with intracellular microelectrodes indicates that 5-HT mimics the action of the transmitter responsible for eliciting slow epsps in one of the types of enteric neuron (the AH cell). In addition, Julé has determined that enteric serotonergic neurons are involved in the descending suppression of vagal excitation of the gut that accompanies peristalsis (67). Since the neurons that contain 5-HT survive for extended periods of time in organotypic tissue culture, it is clear that they are intrinsic to the gut itself. It may now be assumed, therefore, that there are enteric serotonergic neurons. Questions now arise as to their role in gastrointestinal function and the cellular biology of this neuronal class.