Nanomolar concentrations of neuropeptides induce histamine release from peritoneal mast cells of a substrain of Wistar rats

Abstract

Substance P causes histamine release from rat peritoneal mast cells probably through direct activation of a specific G protein at micromolar concentrations. We found that peritoneal mast cells of a substrain of Wistar rats (Std:Wistar) responds to nanomolar concentrations of substance P by releasing histamine in a concentration-dependent manner. In addition, potent histamine release from peritoneal mast cells of the substrain rats was also induced by neurokinin A in a concentration-dependent fashion. Histamine release induced by low concentrations of substance P was significantly blocked by a tachykinin NK 1 receptor antagonist, CP-96345 [(2 S,3 S)- cis-2-(diphenylmethyl)- N-[(2-methoxyphenyl)-methyl]-1-azabicyclo[2.2.2]octan-3-amine dihydrochloride], whereas that induced by concentrations as high as 10 μM appeared resistant to the antagonist. The concentration-histamine release curve for neurokinin A was parallel-shifted to the right by the drug. A tachykinin NK 2 receptor antagonist, SR-48968 [( S)- N-methyl- N[4-(4-acetylamino-4-phenyl piperadino)-2-(3,4-dichlorophenyl)butyl]benzamide], did not influence release stimulated by substance P and neurokinin A. On the other hand, peritoneal mast cells of Sprague–Dawley and other Wistar rats did not respond to neurokinin A. At over 1 μM but not at nanomolar concentrations, substance P caused modest histamine release from peritoneal mast cells of these rats. The results suggest that neurokinin A and nanomolar, but not micromolar concentrations of substance P stimulate tachykinin NK 1 receptors on the peritoneal mast cells of Std:Wistar rat to release histamine.