Plasma protein extravasation induced by mammalian tachykinins in rat skin: influence of anaesthetic agents and an acetylcholine antagonist

Abstract

1 The effect of mammalian tachykinins on plasma protein extravasation was assessed in the rat dorsal skin. Substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) increased vascular permeability in a dose-related manner with a threshold dose of about 0.07 pmol in sodium pentobarbitone-anaesthetized animals. 2 Plasma protein extravasation induced by the tachykinins was 100–500 times less in magnitude in animals anaesthetized with urethane. 3 Plasma protein extravasation induced by SP (66 pmol) was significantly reduced (63%; P < 0.001) by atropine (a muscarinic inhibitor) while that induced by NKA or NKB was unaffected by the inhibitor suggesting that a cholinergic component might only be involved in the vascular permeability elicited by SP. 4 The rank order of potency for the tachykinins on plasma protein extravasation was: NKB > SP > NKA (in absence of atropine) and NKB > NKA > SP (in presence of atropine), suggesting that this vascular response is mediated by a SP-E-receptor type. 5 The amplitudes of the plasma protein extravasation induced by NKB and its hydrophilic analogue [Arg^°]NKB were similar, indicating that the lipophilic features of the native peptide cannot account for its potent biological activity. 6 Plasma protein extravasation was enhanced by the SP analogue [d-Pro⁴, Lys⁶, d-Trp^7,9,10, Phe¹¹] SP (4–11), thus showing the limitation of such SP analogues (antagonists) for characterizing the tachykinin receptors involved in vascular permeability.