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

1. 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 neurones of the isolated inferior mesenteric ganglion. 2. 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 henceforth the non-cholinergic excitatory potential. 3. When the membrane potential was manually clamped, the non-cholinergic potential was associated with three types of membrane resistance change: an increase, a delayed increase and a biphasic change consisting of an initial decrease followed by an increase. 4. In the majority of neurones, conditioning hyperpolarization augmented the non-cholinergic depolarization; in a few neurones, moderate hyperpolarization depressed the latter, whereas stronger hyperpolarization unmasked a low depolarization. 5. The non-cholinergic response was markedly attenuated in the presence of exogenously applied substance P; it was partially suppressed by luteinizing hormone-releasing hormone. 6. Non-cholinergic depolarization could be elicited in the same neurone by stimulation of all four nerve trunks associated with the ganglion. 7. It is suggested that substance P, a peptide, may be the transmitter responsible for the generation of the non-cholinergic potential and that it may be released from collateral endings of primary sensory neurones, thus providing a functional connexion between sensory and autonomic neurones.