The tachykinin NK1 receptor antagonist, RP67580, inhibits the bradykinin-induced rise in intracellular Ca2+ concentration in bovine pulmonary artery endothelial cells

Vlieger, Janneke F Westra-De; Wijngaard, Paul W.J Van Den; Koster, Andries S.; Wilting, Jaap; Leysen, J E; Heuven-Nolsen, D. van; Nijkamp, Frans P.

doi:10.1016/s0014-2999(97)01506-9

Cited by 2 publications

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“…Several previous studies reported the inhibition of plasma exudation during neurogenic inflammation by different NK 1 receptor antagonists which block the effects of substance P on the vascular permeability (see for instance: Lembeck et al 1982;Andrews et al 1989;Garret et al 1991;Lembeck et al 1992;Moussaoui et al 1993). Whereas RP67580 was sometimes described as a blocker of calcium channels (Rupniak et al 1993;Westra-De Vlieger et al 1998), the fact that its negative enantiomer, RP68651, has only a suppressive effect at very large doses indicates that the antagonism of substance P by RP67580 is specifically involved in the inhibition of formalin oedema. In the same way, plasma extravasation in rat paws was reduced 10 and 50 min after formalin used at a low dose (1%) by a µ-opioid receptor agonist (Hong and Abbott 1995) which inhibits the release of substance P from primary afferent neurons (Lembeck and Donnerer 1985).…”

Section: Discussionmentioning

confidence: 99%

The inflammatory reaction induced by formalin in the rat paw

Damas

Liégeois

1999

Naunyn-Schmiedeberg's Arch Pharmacol

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The involvement of bradykinin and some other inflammatory mediators in formalin-induced oedema and plasma extravasation was examined. Formalin was injected in rat paws at two doses, 1.75% or 5%. The lower dose induced the development of an immediate oedema associated with a progressive accumulation of 125I-labelled albumin in the paws. These changes were suppressed by pretreatment with capsaicin or xylocaine. They were abolished by RP67580, a NK1 receptor antagonist, and increased by phosphoramidon or diprotin A. They were not affected by HOE140, a bradykinin B2 antagonist, captopril, methysergide, mepyramine, indomethacin, ketoprofen or L-N(G)-nitroarginine. The higher dose of formalin induced a swelling of the paws which took place in two phases associated with two periods of increase in vascular permeability. This oedema was reduced by pretreatment with capsaicin but not with xylocaine. It was reduced by RP67580 injected before or 30 min after formalin. It was inhibited by mepyramine, methysergide, indomethacin and NS-398, a cyclooxygenase-2 inhibitor. It was not modified by HOE140. Its development was similar in normal and kininogen-deficient rats. We concluded that formalin administered at a low dose induces an oedema which mainly results from a neurogenic inflammation mediated by neuropeptides such as substance P. At higher doses, formalin induces an oedema which mainly depends on the release of substance P, prostanoids, 5-hydroxytryptamine and histamine. Bradykinin plays no significant role in the vascular changes whereas this peptide has been reported to participate in the stimulation of nociceptive afferent neurons. This discrepancy could be explained by a difference in the threshold of stimulation of the nociceptive neurons and that of the cells of the vascular walls, or by a formation of kinins in close contact of the neurons.

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