Acetylcholine and substance P: Action via distinct receptors on carp retinal ganglion cells

Substance P (SP), a neuropeptide, has been found in amarcine cells in a variety of vertebrate retinas. SP excited many of the ganglion cells we sampled in carp retina; many of these ganglion cells are directly excited by cholinergic agonists. It has been reported that SP modulates cholinergic synaptic transmission in some other neuronal systems by inhibiting or desensitizing cholinergic receptors. SP does not act in this way on the ganglion cell cholinergic receptors in isolated carp retina. Pulses of acetylcholine (ACh), applied to sensitive ganglion cells by microiontophoresis, were set to elicit consistent cellular responses. Application of SP to the retina through a nebulizing system (final concentration about 10^-6 M) did not reduce the excitation produced by the ACh pulse. In earlier work, we showed that the cholinergic receptores were nicotinic; in the present study, SP occasionally excited cells after the retina was treated with a nicotinic cholinergic antagonist, gallamine triethiodide. SP appears to excite cholinergic-sensitive ganglion cells at a postsynaptic site other than their nicotinic cholinergic receptor and via a pathway that does not require a presynaptic, SP-sensitive, ACh-releasing interneuron.