Substance P enhances cation permeability of neuronal cell lines.
Substance P stimulated the uptake of guanidinium in neuroblastoma X glioma hybrid cells and neuroblastoma cells but not in polyploid glioma cells. Guanidinium has previously been shown to pass the action potential Na+ channel in the two neuronal cell lines. Half-maximal stimulation was reached at 3 microM substance P and, with the hybrid cells, a saturation was seen above 10 microM. The analogue (D-Pro2,D-Trp7,9)-substance P, recently described as a substance P antagonist, caused a stimulation of guanidinium uptake comparable to that seen in the presence of substance P and did not inhibit the stimulation exerted by substance P. The pharmacological properties of the substance P-activated ion channel were investigated. Tubocurarine, phentolamine and propranolol blocked the substance P-stimulated guanidinium uptake with half-maximal inhibitory concentrations of 0.5, 5 and 50 microM. A similar characteristics has been found previously with the veratridine-activated Na+ channel in the cell lines investigated here. Peptides structurally related to substance P such as physalaemin and eledoisin, or others such as neurotensin, bradykinin, D-Ala2, Met5-enkephalinamide and ACTH(1-24) did not affect guanidinium uptake. In view of the high concentrations of substance P required for eliciting an effect in the cell lines, the involvement of specific receptors is questioned. A direct interaction of the peptide with the action potential Na+ channel is discussed.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D005910:Glioma / Q000378:metabolism*; D019791:Guanidine; D006146:Guanidines / Q000378:metabolism; D006822:Hybrid Cells / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*
D006146:Guanidines; D007473:Ion Channels; D013373:Substance P; D012964:Sodium; D019791:Guanidine