Mechanisms of T-kinin-induced increases in macromolecule extravasation in vivo.
The purpose of this study was to investigate the mechanisms that mediate T-kinin- (Ile-Ser-bradykinin) induced increases in macromolecule extravasation in the hamster cheek pouch. Changes in plasma extravasation were quantified by counting the number of leaky sites and calculating the clearance of fluorescein isothiocyanate- (FITC) dextran (mol mass = 70 kDa) during suffusion of the cheek pouch with T-kinin (0.1-1.0 microM) by using intravital microscopy. T-kinin induced a significant time- and concentration-dependent increase in leaky site formation and clearance of FITC-dextran (P < 0.05). The increase in plasma extravasation in response to T-kinin was mediated by two mechanisms: a COOH-terminal-mediated stimulation of B2 bradykinin receptors in postcapillary venules and an NH2-terminal-mediated degranulation of mast cells leading to histamine release. Indomethacin and CP 96345, a selective nonpeptide neurokinin-1 receptor antagonist, had no significant effects on T-kinin-induced responses. We conclude that T-kinin increases macromolecule extravasation in the peripheral microcirculation by stimulating B2 bradykinin receptors in post-capillary venules and by degranulating mast cells.
Gao
X P
XP
Department of Internal Medicine, University of Nebraska Medical Center, Omaha.
Mayhan
W G
WG
Conlon
J M
JM
Rennard
S I
SI
Rubinstein
I
I
D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology; D006224:Cricetinae; D003911:Dextrans / Q000493:pharmacokinetics; D004487:Edema / Q000209:etiology* / Q000503:physiopathology; D016650:Fluorescein-5-isothiocyanate / Q000493:pharmacokinetics / Q000031:analogs & derivatives; D006633:Histamine Antagonists; D007213:Indomethacin / Q000494:pharmacology; D046911:Macromolecular Substances; D008297:Male; D008647:Mesocricetus; D008969:Molecular Sequence Data; D018002:Receptors, Bradykinin; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D003911:Dextrans; D006633:Histamine Antagonists; D046911:Macromolecular Substances; D018002:Receptors, Bradykinin; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; C015219:fluorescein isothiocyanate dextran; D003189:p-Methoxy-N-methylphenethylamine; C039065:T-kinin; D016650:Fluorescein-5-isothiocyanate; D001920:Bradykinin; D007213:Indomethacin