NK2 receptors mediate plasma extravasation in guinea‐pig lower airways

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.