Specific neurokinin receptors mediate plasma extravasation in the rat knee joint

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Abstract
1 Plasma extravasation in the rat knee joint was induced by intra-articular injection of neurokinins and specific neurokinin receptor agonists. 2 Pronounced plasma extravasation was produced by substance P (SP, 4–185 μm) and to a lesser extent by neurokinin-B (NKB, 83–413 μm), whereas neurokinin-A (NKA, 88–440 μm) and calcitonin gene-related peptide (CGRP, 26–130 μm) had no significant effect. 3 The specific neurokinin1 receptor agonist [Sar9, Met(O2)11]-substance P (NR1 agonist) in doses of 0.4–70 μm appeared to be more potent than SP in eliciting plasma extravasation. The neurokinin2 receptor agonist [Nle10]-neurokinin A4–10 (NK2 agonist) was not effective at 70 μm but produced a small and significant effect at 330 μm, whereas the neurokinin3 receptor agonist [MePhe7]-neurokinin B (NK3 agonist) was without effect at 40 μm or 400 μm. 4 Injections of SP or NKA into the synovial cavity of the rat knee were equally effective in producing marked plasma extravasation in remote sites such as the forelimb and hindlimb paws. 5 Co-administration experiments showed that the effects of SP were synergistic with NKA or the NK1 receptor agonist, but not with CGRP or the NK2 receptor agonist. 6 The rank order of potency was NK1 agonist ≥ SP > NKB > NK2 agonist suggesting that NK1 receptors mediate plasma extravasation in the rat knee joint.