Receptor subtypes involved in tachykinin-mediated edema formation☆

Abstract

Intradermal (ID) injection of the natural tachykinins substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) (0.3–30 nmol) resulted in a marked and dose-related rat paw edema, with mean ED 50 values of 2.68 nmol, 1.17 nmol, and 0.80 nmol, respectively. The ID injection of the selective NK 1, SP methyl-ester (1–30 nmol), NK 2, [β-Ala 8]-neurokinin A 4–10 (β-Ala, 0.3–30 nmol), or NK 3, senktide (1–10 nmol) agonists, caused extensive edema formation with mean ED 50s of 0.48 nmol, 0.41 nmol, and 0.18 nmol, respectively. The ID injection of the selective NK 1 antagonist FK888 (0.1–3 nmol) produced marked inhibition (94%, 52%, and 66%, respectively) of rat paw edema induced by SP, NKA, or SP methyl-ester. The ID co-injection of the NK 2 receptor antagonist SR 48968 elicited a graded inhibition (52%, 67%, and 35%, respectively) of rat paw edema induced by NKA, β-Ala and, to a lesser extent, the edema caused by SP. Finally, the ID co-injection of the NK 3 receptor antagonist SR 142801 significantly inhibited (53%, 76%, 53%, and 100%, respectively) the edema formation caused by NKB and NKA or by SP and senktide. Together, the data of the present study suggest that tachykinin-mediated rat paw edema depends on the activation of NK 1, NK 2 and NK 3 receptor subtypes, with apparent major involvement of NK 1 receptors subtypes.