Nanomolar concentrations of neuropeptides induce histamine release from peritoneal mast cells of a substrain of Wistar rats.
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 NK1 receptor antagonist, CP-96345 [(2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)-methyl]-1-aza bicyclo[2.2.2]octan-3-amine dihydrochloride], whereas that induced by concentrations as high as 10 microM appeared resistant to the antagonist. The concentration-histamine release curve for neurokinin A was parallel-shifted to the right by the drug. A tachykinin NK2 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 microM 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 receptors on the peritoneal mast cells of Std:Wistar rat to release histamine.
Ogawa
K
K
Department of Pharmacology, Kyoto Pharmaceutical University, Yamashina, Japan.
Nabe
T
T
Yamamura
H
H
Kohno
S
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release / Q000187:drug effects*; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D015288:Neurokinin A / Q000494:pharmacology*; D010537:Peritoneum / Q000166:cytology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013045:Species Specificity; D013373:Substance P / Q000494:pharmacology*; D015320:Tachykinins / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001549:Benzamides; D001713:Biphenyl Compounds; D010880:Piperidines; D015320:Tachykinins; D013373:Substance P; C073839:SR 48968; D015288:Neurokinin A; C066892:CP 96345