Receptor subtypes involved in tachykinin-mediated edema formation

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 ED50 values of 2.68 nmol, 1.17 nmol, and 0.80 nmol, respectively. The ID injection of the selective NK1, SP methyl-ester (1-30 nmol), NK2, [beta-Ala(8)]-neurokinin A(4-10) (beta-Ala, 0.3-30 nmol). or NK3, senktide (1-10 nmol) agonists, caused extensive edema formation with mean ED(50)s of 0.48 nmol, 0.41 nmol, and 0.18 nmol, respectively. The ID injection of the selective NK1 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 NK2 receptor antagonist SR 48968 elicited a graded inhibition (52%, 67%, and 35%, respectively) of rat paw edema induced by NKA, beta-Ala and, to a lesser extent, the edema caused by SP. Finally, the ID co-injection of the NK3 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 NK1, NK2 and NK3 receptor subtypes, with apparent major involvement of NK1 receptors subtypes. (C) 1999 Elsevier Science Inc. All ri hts reserved.