The physiology of substance P in the rabbit retina

The neuropeptide substance P (SP) has been localized to amacrine and ganglion cells in the rabbit retina. We have examined the effects of SP and related peptides on rabbit retinal neurons using bath application and intra- and extra-cellular electrophysiological methods in an in vitro retina eyecup preparation. Substance P, at concentrations as low as 25 nM, moderately excited most brisk ganglion cells. SP excited some ganglion cells directly during cobalt block of synaptic transmission. Intracellular recordings from amacrine cells demonstrated that some, but not all, were depolarized by SP; pharmacological evidence suggested GABAergic amacrines were probably among those sensitive to SP. SP did not affect horizontal cells or the ERG, suggesting that the effects of this peptide are confined to the inner retina. The effects of SP were strongly potentiated by peptidase inhibitors, raising the possibility that endogenously released SP may act quite locally in the rabbit retina. The relative potencies of SP and the related peptides substance K and eledoisin on different cells suggest that more than one tachykinin receptor subtype is present in the rabbit retina. The responses of ganglion cells to SP desensitized with repeated or prolonged applications. Comparison of a cell's light responses before and after the receptors were desensitized revealed no qualitative changes in receptive field characteristics, but quantitative changes in excitability were apparent. SP antagonist analogs, although not potent, specifically blocked the effects of SP on some ganglion cells. The effects of these antagonists on light responses reinforced the inferences from desensitization paradigms regarding the role of endogenous SP. The results of this study suggest that SP does not participate in shaping the characteristic receptive field properties of ganglion cells, but SP - or related peptides - may modulate the excitability of inner retinal neurons.