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0026-895X/97/010120-08$3.00/0
Copyright © by The American Society for Pharmacology and Experimental Therapeutics
All rights of reproduction in any form reserved.
MOLECULAR PHARMACOLOGY 52:120-127 (1997).

High Affinity Binding of [3H]Propionyl-[Met(O2)11]Substance P(7-11), a Tritiated Septide-Like Peptide, in Chinese Hamster Ovary Cells Expressing Human Neurokinin-1 Receptors and in Rat Submandibular Glands

Sandrine Sagan, Jean-Claude Beaujouan, Yvette Torrens, Monique Saffroy, Gérard Chassaing, Jacques Glowinski, and Solange Lavielle

Laboratoire de Chimie Organique Biologique, URA CNRS 493, Université Pierre et Marie Curie, 75252 Paris Cedex 05, France (S.S., G.C., S.L.), and Chaire de Neuropharmacologie, Institut National de la Santé et de la Recherche Médicale U114, Collège de France, 75005 Paris, France (J.-C.B., Y.T., M.S., J.G.)

Propionyl-[Met(O2)11]substance P(7-11) [ALIE-124 or propionyl-[Met(O2)11]SP(7-11)] has been designed as a septide-like ligand adequate for tritiation and, therefore, adequate for binding studies. In Chinese hamster ovary (CHO) cells expressing human tachykinin neurokinin (NK)-1 receptors, ALIE-124 displaced [3H][Pro9]substance P (SP) from its binding site at micromolar concentrations. However, ALIE-124 stimulated phosphatidylinositol hydrolysis, as previously shown for septide-like peptides. With [3H]ALIE-124 (95 Ci/mmol), we have been able to reveal a high affinity binding site in CHO cells (Kd = 6.6 ± 1.0 nM), with a low maximal binding capacity. [3H]ALIE-124 specific maximal binding represented only 15-20% of that observed with [3H][Pro9]SP in CHO cells. Septide-like peptides, including septide and NKA, were potent competitors (in the nanomolar range) of [3H]ALIE-124 specific binding site. Interestingly, SP and [Pro9]SP were also potent competitors, with 10-fold greater potency for sites labeled with [3H]ALIE-124 than for sites labeled with [3H][Pro9]SP. The NK-1 antagonist RP 67580 also showed a higher potency for [3H]ALIE-124 than for [3H][Pro9]SP-specific binding sites. NKB and [Lys5,methyl-Leu9,Nle10]NKA(4-10) displaced [3H]ALIE-124 binding but with lower potency, whereas senktide had no affinity. The existence of [3H]ALIE-124 specific binding sites was also demonstrated in rat submandibular gland. In this tissue, [3H]ALIE-124 specific maximal binding was higher, reaching 40-50% of that achieved with [3H][Pro9]SP.

Copyright © by The American Society for Pharmacology and Experimental Therapeutics


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