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This study aimed to characterise the receptors underlying the activation of the mucosal terminals of the myenteric intrinsic primary afferent neurons by the putative sensory mediators 5HT and ATP. Guinea pigs were stunned by a blow to the head and killed by severing the carotid arteries and spinal cord. Intracellular recordings were made in vitro from AH neurons and some S neurons located within 1 mm circumferential to intact mucosa during pressure ejection of agonists onto small regions of the mucosal surface; antagonists were applied via superfusion into the recording chamber. Trains of action potentials (APs) and/or slow EPSP-like responses were recorded in AH neurons in response to application of 5HT, 2methyl 5HT (5HT3) and ATP. No responses were recorded in response to application of the -methyl 5HT (5HT2), 5methyoxytryptamine (5HT1,2,4) or ,-methylene ATP. All responses elicited by 5HT and 2-methyl 5HT were blocked by the 5-HT receptor antagonists granisetron (5HT3 receptors) or tropisetron (5HT3,4) but not by SB 204,070 (5HT4); all at 1 M. Neither the 5-HT receptor antagonist, granisetron, nor the P2X receptor antagonists, suramin or PPADS (both at 30 M), blocked the responses to ATP. It is concluded that the mucosal processes of the AH neurons in the guinea pig small intestine possess functional 5HT3 receptors and either an atypical P2X receptor or a P1 receptor. Activation of these receptors causes AP generation in the mucosal process of the sensory neuron which then propagates to the cell body and to the other processes located in the myenteric and submucosal ganglia.