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.
Tousignant
C
C
Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, Québec, Canada.
Chan
C C
CC
Guevremont
D
D
Brideau
C
C
Hale
J J
JJ
MacCoss
M
M
Rodger
I W
IW
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