title: Characterization of a substance P receptor activating a cation permeability in neuronal cell lines.
abstract: Substance P at micromolar concentrations enhances the uptake of [14C]guanidinium in neuroblastoma X glioma hybrid cells, an effect which most likely indicates activation of Na+ permeability. The substance P receptor was characterized pharmacologically. Analogues of substance P with D-amino acids e.g. spantide, and substance P-methyl ester were similarly active. Substance P (free acid), fragments of the substance P precursor, and substance P-(1-9) displayed no activity. This indicates the importance of the hydrophobic C-terminal for stimulation of the hybrid cells. The potency was reduced with decreasing length the of C-terminal fragments. However, the substance P antagonists [D-Pro4,D-Trp7,9,Nle11]substance P-(4-11) and [D-Pro4,D-Trp7,9,10]substance P-(4-11) showed substantially greater activity than substance P-(4-11). Substance P-(6-11) (i.e. H-Arg-DTrp-MePhe-DTrp-Leu-Met-NH2) behaved as a mixed agonist-antagonist. At concentrations higher than 10 microM, it inhibited the stimulation exerted by substance P. No other peptides of the tachykinin family (neurokinins A and B, physalaemin, eledoisin, kassinin) nor the synthetic analogues with specificity for certain receptor subtypes ([pGlu6,Pro9]substance P-(6-11), DiMe-C7, i.e. [pGlu5,MePhe8,Sar9]substance P-(5-11) and senktide, i.e. N-succinyl-[Asp6,MePhe8]substance P-(6-11) had any effect on guanidinium uptake in the hybrid cells. Hence, the substance P site with low affinity on the hybrid cells does not fit into the usual classification of tachykinin receptors but resembles the site that modulates nicotinic acetylcholine receptors on chromaffin cells.
mesh_terms: D005910:Glioma; D019791:Guanidine; D006146:Guanidines / Q000493:pharmacokinetics*; D006822:Hybrid Cells; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism*; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D006146:Guanidines; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P; D019791:Guanidine