Substance P Modulates Cholinergic Regulation of the Nicotinic Acetylcholine Receptor of PC12 Cells

Of the diverse roles that have been proposed for neuropeptides, modulation of the activity of other neurotransmitter receptors is particularly interesting in view of the coexistence of peptides and conventional neurotransmitters in many neuronal structures (1). An example of peptidergic modu1ation that has been well studied is the inhibition of nicotinic cholinergic receptor function by SP. Reported initially for cat Renshaw cells (2) and the Mauthner fibre-giant fibre synapse of hatchet fish (3) and subsequently in more detail for the clonal cell line PC12 (4), adrenal chromaffin cells (5) and sympathetic ganglion cell s (6), this inhibitory action by SP appears to reflect an enhancement of AcCh receptor desensitization.