NK2 receptors mediate plasma extravasation in guinea-pig lower airways.
1. Neurokinin (NK) receptor-mediated extravasation has been examined in guinea-pig airways by use of a recently described marker for microvascular protein leakage, 125I-labelled human fibrinogen. 2. Neurokinin A (NKA) caused a dose-dependent increase in plasma [125I]-fibrinogen extravasation in trachea, main bronchi, secondary bronchi and intraparenchymal airways. In contrast, the NK2 selective agonist [beta-Ala8]NKA(4-10) only caused extravasation in the secondary and intraparenchymal airways. 3. The NK2 selective antagonist, SR 48968, caused a dose-dependent inhibition of NKA and [beta-Ala8]NKA(4-10)-induced extravasation of fibrinogen in guinea-pig secondary bronchi and intraparenchymal airways. SR 48968 was without effect on the NKA-induced extravasation in trachea and main bronchi. 4. NKA- or [beta-Ala8]NKA(4-10)-induced plasma extravasation was not modified by pretreatment with histamine H1- or H2-receptor antagonists. 5. It is concluded that NK2 receptors mediate plasma [125I]-fibrinogen extravasation in guinea-pig secondary bronchi and intraparenchymal airways. This effect is direct and does not depend upon histamine released from mast cells.
Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, Québec, Canada.
C
C
Tousignant
C C
CC
Chan
D
D
Guevremont
C
C
Brideau
J J
JJ
Hale
M
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MacCoss
I W
IW
Rodger
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001798:Blood Proteins / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects*; D005119:Extravasation of Diagnostic and Therapeutic Materials; D006168:Guinea Pigs; D007457:Iodine Radioisotopes; D008297:Male; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*
D001549:Benzamides; D001798:Blood Proteins; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D010880:Piperidines; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; C064218:neurokinin A (4-10), beta-Ala(8)-; C073839:SR 48968; D015288:Neurokinin A