Stimulation of angiogenesis by substance P and interleukin‐1 in the rat and its inhibition by NK1 or interleukin‐1 receptor antagonists
TPD Fan, DE Hu, S Guard… - British journal of …, 1993 - Wiley Online Library
TPD Fan, DE Hu, S Guard, GA Gresham, KJ Watling
British journal of pharmacology, 1993•Wiley Online Library1 Daily administration of 1 nmol substance P or 3 pmol recombinant human interleukin‐1
alpha (IL‐1α) caused intense neovascularization in a rat sponge model of angiogenesis.
Lower doses of substance P (10 pmol) or IL‐1α (0.3 pmol) were ineffective when given
alone. When combined at these low doses, substance P and IL‐1α interacted to produce an
enhanced neovascular response. 2 By use of selective tachykinin NK1, NK2 and NK3
receptor agonists,([Sar9, Met (O2) 11] substance P,[β‐Ala8] neurokinin A (4–10), Succ …
alpha (IL‐1α) caused intense neovascularization in a rat sponge model of angiogenesis.
Lower doses of substance P (10 pmol) or IL‐1α (0.3 pmol) were ineffective when given
alone. When combined at these low doses, substance P and IL‐1α interacted to produce an
enhanced neovascular response. 2 By use of selective tachykinin NK1, NK2 and NK3
receptor agonists,([Sar9, Met (O2) 11] substance P,[β‐Ala8] neurokinin A (4–10), Succ …
- 1Daily administration of 1 nmol substance P or 3 pmol recombinant human interleukin‐1 alpha (IL‐1α) caused intense neovascularization in a rat sponge model of angiogenesis. Lower doses of substance P (10 pmol) or IL‐1α (0.3 pmol) were ineffective when given alone. When combined at these low doses, substance P and IL‐1α interacted to produce an enhanced neovascular response.
- 2By use of selective tachykinin NK1, NK2 and NK3 receptor agonists, ([Sar9,Met(O2)11]substance P, [β‐Ala8]neurokinin A(4–10), Succ‐[Asp6,MePhe8]substance P(6–11) (senktide), respectively), it was established that the activation of NK1 receptors is most likely to mediate the angiogenic response to substance P in this model.
- 3The angiogenic activity of substance P and IL‐1α (10 pmol and 0.3 pmol day−1, respectively) was abolished by co‐administration of (i) the selective peptide NK1 receptor antagonist, L‐668,169 (1 nmol day−1), (ii) the selective non‐peptide NK1 receptor antagonists, RP 67580 and (±)‐CP‐96,345 (both at 1 nmol day−1) or (iii) the IL‐1 receptor antagonist, IL‐1ra, (50 μg day−1). In contrast, the selective NK2 receptor antagonist, L‐659,874 (1 nmol day−1) was ineffective.
- 4The angiogenic action of substance P and IL‐1α was resistant to modification by mepyramine (1 nmol day−1) and/or cimetidine (10 nmol day−1), indomethacin (7 nmol day−1) or the platelet‐activating factor (PAF) antagonist, WEB‐2086 (22 nmol day−1), indicating that histamine, prostaglandins and PAF are not likely to be involved in this neovascular response.
- 5The inhibition of the substance P/IL‐1 angiogenic response by selective NK1 receptor antagonists or by an IL‐1 receptor antagonist demonstrates that angiosuppression can be achieved by blocking the activity of angiogenic factors at the receptor level.
Wiley Online Library