Comparison of the effects of neurokinin-3 receptor blockade on two forms of slow synaptic transmission in myenteric AH neurons

AH neurons are intrinsic sensory neurons of the intestine that exhibit two types of slow synaptic event: slow excitatory postsynaptic potentials which increase their excitability fur about 2-4 min. and sustained slow postsyna ptic excitation which can persist for several hours, and may be involved in long-term changes in the sensitivity of the intestine to sensory stimuli. The effects of the neurokinin-3 tachykinin receptor antagonist. SR142801, o n these two types of synaptic event in AH neurons of the myenteric ganglia of guinea-pig small intestine were compared. Slow excitatory postsynaptic p otentials were evoked by stimulation of synaptic inputs at 10-20 Hr for 1 s . and sustained slow postsynaptic excitation was evoked by stimulation of i nputs at 1 Hz for 4 min. SR142801 (1 muM) reduced the amplitude of the slow excitatory post synaptic potential to 26% of control, and also reduced the increase in input resistance and the extent of anode break excitation asso ciated with the slow excitatory postsynaptic potential, In contrast. SR1428 01 did not reduce the increase in excitability, the increase in input resis tance or the depolarisation that occur during the sustained slow postsynapt ic excitation. SR142801 did nor change the resting membrane potential or th e resting input resistance. We conclude that tachykinins. acting through neurokinin-3 receptors, are in volved in the generation of the slow excitatory postsynaptic potential, bur not in the sustained slow postsynaptic excitation, and that the release of transmitters from synaptic inputs to AH neurons is frequency coded. (C) 20 01 IBRO. Published by Elsevier Science Ltd, All rights reserved.