Plasma extravasation induced by neurokinins in conscious rats: receptor characterization with agonists and antagonists.
The purpose of the present experiments was to study the effects of various neurokinin related peptides, such as substance P, [beta Ala8]NKA(4-10), and [MePhe7]NKB, which are selective for NK-1, NK-2, and NK-3 functional sites, respectively, to induce plasma extravasation in rats and the effectiveness of RP 67580 and CP-96,345 (two nonpeptide NK-1 receptor selective antagonists) and SR 48968 (a nonpeptide NK-2 receptor selective antagonist) to prevent such an effect. Bolus intravenous injection of substance P (1.0 nmol/kg) into conscious rats induced extravasation of Evans blue dye (EB), a selective marker of albumin vascular permeability, in the duodenum, the stomach, the pancreas, and the urinary bladder by 50, 40, 58, and 312%, respectively; a slight increment occurred also in the ileum and the kidney but was not significant. [beta Ala8]NKA(4-10) (1.0 nmol/kg) increased EB extravasation in the stomach and the urinary bladder by 52 and 99%, respectively, while [MePhe7]NKB (1.0 nmol/kg) did the same in the stomach, the ileum, and the urinary bladder by 58, 50, and 79%. Pretreatment with RP 67580 (250 nmol/kg) blocked the albumin extravasation mediated by substance P in the duodenum, the pancreas, and the urinary bladder by 100, 100, and 78%, respectively. CP-96,345 (250 nmol/kg) also inhibited EB extravasation mediated by substance P in the duodenum and the pancreas by 100 and 100%, respectively, but was ineffective in the urinary bladder. Neither RP 67580 nor CP-96,345 prevented the substance P mediated extravasation in the stomach. RP 67580 and CP-96,345 did not antagonize the effects of NK-2 and NK-3 selective agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
Nicolau
M
M
Department of Pharmacology, Medical School, Université de Sherbrooke, PQ, Canada.
Sirois
M G
MG
Bui
M
M
Plante
G E
GE
Sirois
P
P
Regoli
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects*; D003243:Consciousness; D005070:Evans Blue / Q000493:pharmacokinetics; D005119:Extravasation of Diagnostic and Therapeutic Materials; D007211:Indoles / Q000494:pharmacology; D007275:Injections, Intravenous; D054833:Isoindoles; D008297:Male; D008969:Molecular Sequence Data; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D015287:Neurokinin B / Q000031:analogs & derivatives; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors* / Q000502:physiology*; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors* / Q000502:physiology*; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*
D001549:Benzamides; D001713:Biphenyl Compounds; D001798:Blood Proteins; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D015320:Tachykinins; C080394:neurokinin B, MePhe(7)-; C064218:neurokinin A (4-10), beta-Ala(8)-; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D005070:Evans Blue; C073839:SR 48968; D015288:Neurokinin A; D015287:Neurokinin B; C066892:CP 96345