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

British Journal of Pharmacology - Tập 91 Số 2 - Trang 265-273 - 1987
Réjean Couture1, René Kérouac1
1Département de Physiologie, CRSN, Faculté de Médecine, Université de Montréal, C.P. 6208, Succursale A, Montréal, Québec, Canada H3C 3T8

Tóm tắt

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. Plasma protein extravasation induced by the tachykinins was 100–500 times less in magnitude in animals anaesthetized with urethane. 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. 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. 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. Plasma protein extravasation was enhanced by the SP analogue [d‐Pro4, Lys6, d‐Trp7,9,10, Phe11] SP (4–11), thus showing the limitation of such SP analogues (antagonists) for characterizing the tachykinin receptors involved in vascular permeability.

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British Journal of Pharmacology

Tập 91 Số 2

265-273

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