Non‐cholinergic excitatory transmission in inferior mesenteric ganglia of the guinea‐pig: possible mediation by substance P.

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Abstract
Repetitive stimulation of guinea pig hypogastric nerves elicited, in addition to the fast cholinergic excitatory potential, a slow depolarization lasting for seconds to minutes in neurons of the isolated inferior mesenteric ganglion. The slow depolarization which could be elicited at a frequency as low as 1-2 Hz for several seconds was not blocked by cholinergic antagonists, but was eliminated in a low Ca2+ solution; it was termed the noncholinergic excitatory potential. When the membrane potential was manually clamped, the noncholinergic potential was associated with 3 types of membrane resistance change: an increase, a delayed increase anbd a biphasic change consisting of an initial decrease followed by an increase. In a majority of neurons, conditioning hyperpolarization augmented the noncholinergic depolarization; in a few neurons, moderate hyperpolarization depressed the latter, whereas stronger hyperpolarization unmasked a low depolarization. The noncholinergic response was markedly attenuated in the presence of exogenously applied substance P; it was partially suppressed by LHRH. Noncholinergic depolarization could be elicited in the same neuron by stimulation of all 4 nerve trunks associated with the ganglion. Substance P, a peptide, may be the transmitter responsible for the generation of the noncholinergic potential and it may be released from collateral endings of primary sensory neurons, thus providing a functional connection between sensory and autonomic neurons.