PT  - JOURNAL ARTICLE
AU  - S M Simasko
AU  - J R Soares
AU  - G A Weiland
TI  - Structure-activity relationship for substance P inhibition of carbamylcholine-stimulated 22Na+ flux in neuronal (PC12) and non-neuronal (BC3H1) cell lines.
DP  - 1985 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 601--605
VI  - 235
IP  - 3
4099  - http://jpet.aspetjournals.org/content/235/3/601.short
4100  - http://jpet.aspetjournals.org/content/235/3/601.full
SO  - J Pharmacol Exp Ther1985 Dec 01; 235
AB  - The inhibition of carbamylcholine-stimulated 22Na+ flux by substance P and various peptide analogs was examined in PC12 cells, a line which contains a neuronal-type nicotinic receptor, and BC3H1 cells, a line which contains a muscle-type nicotinic receptor. Substance P produces a noncompetitive inhibition of carbamylcholine-stimulated 22Na+ influx in both cell lines (IC50 = 1.2 microM on PC12 cells and 8.2 microM on BC3H1 cells). The structure-activity relation for substance P analogs was qualitatively similar in both cell lines; however, there were quantitative differences. Substance P was the most potent peptide tested. Analogs of substance P with amino acids removed from the N-terminus resulted in significant decreases in potency, whereas removal of amino acids from the C-terminus resulted in analogs virtually devoid of activity. Compounds purported to be substance P antagonists had actions similar to substance P in reducing carbamylcholine-stimulated 22Na+ flux. The related tachykinins physalaemin and eledoisin had low potencies on both cell lines. These results indicate that the site through which substance P exerts its inhibitory effects on activation of nicotinic receptors is different from the receptors described previously for substance P in more classical systems. In addition, our results indicate that substance P has an effect on both the neuronal-type nicotinic receptor (alpha-bungarotoxin insensitive) expressed on PC12 cells and the muscle-type nicotinic receptor (alpha-bungarotoxin sensitive) expressed on BC3H1 cells.