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 [β‐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 [β‐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 [β‐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.