PMID- 1701206 OWN - NLM STAT- MEDLINE DCOM- 19910115 LR - 20220331 IS - 0026-2862 (Print) IS - 0026-2862 (Linking) VI - 40 IP - 2 DP - 1990 Sep TI - Substance P stimulates neovascularization in vivo and proliferation of cultured endothelial cells. PG - 264-78 AB - We have investigated the possible effect of substance P (SP), a main mediator of neurogenic inflammation, on the growth of capillary vessels in vivo, and on the proliferation of cultured endothelial cells in vitro. Slow release preparations of SP were implanted into the avascular cornea of New Zealand White rabbits and vessel growth was monitored daily through a slit lamp stereomicroscope. SP (1-5 micrograms/pellet) induced a marked neovascularization. A selective NK-1 receptor agonist [beta-Ala4, Sar9, Met(O2)11]-SP(4-11) also induced neovascularization. The addition of SP to serum-free cultured endothelial cells, isolated from bovine adrenals (BACE) and from human umbilical cord veins (HUVE), increased proliferation of both cell lines in a concentration-dependent manner with maximal activity at 10(-8) M (BACE) and 10(-10) M (HUVE). The selective NK-1 receptor agonist induced a similar proliferative action on both cell lines, while the selective NK-2 receptor agonist [beta-Ala8]-NKA(4-10) and the selective NK-3 receptor agonist [MePhe7]-NKB had no significant effect. Two different SP antagonists [D-Pro2, D-Trp7,9]-SP and [D-Pro4, D-Trp7,9,Phe11]-SP (4-11) blocked the response to SP. These findings indicate that SP can directly stimulate the process of neovascularization, probably through induction of endothelial cell proliferation. This hitherto unraveled activity of SP could play a key role in the trophic action produced by activation of the efferent function of peripheral endings of primary sensory neurons. FAU - Ziche, M AU - Ziche M AD - Department of Preclinical and Clinical Pharmacology, Mario Aiazzi Mancini, University of Florence, Italy. FAU - Morbidelli, L AU - Morbidelli L FAU - Pacini, M AU - Pacini M FAU - Geppetti, P AU - Geppetti P FAU - Alessandri, G AU - Alessandri G FAU - Maggi, C A AU - Maggi CA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Microvasc Res JT - Microvascular research JID - 0165035 RN - 0 (Receptors, Neurotransmitter) RN - 0 (Receptors, Tachykinin) RN - 0 (Tachykinins) RN - 33507-63-0 (Substance P) SB - IM MH - Animals MH - Cell Division/drug effects MH - Cell Line MH - Endothelium, Vascular/cytology/*drug effects/metabolism MH - *Neovascularization, Pathologic MH - Rabbits MH - Receptors, Neurotransmitter/drug effects/metabolism MH - Receptors, Tachykinin MH - Substance P/antagonists & inhibitors/*pharmacology MH - Tachykinins/metabolism EDAT- 1990/09/01 00:00 MHDA- 1990/09/01 00:01 CRDT- 1990/09/01 00:00 PHST- 1990/09/01 00:00 [pubmed] PHST- 1990/09/01 00:01 [medline] PHST- 1990/09/01 00:00 [entrez] AID - 10.1016/0026-2862(90)90024-l [doi] PST - ppublish SO - Microvasc Res. 1990 Sep;40(2):264-78. doi: 10.1016/0026-2862(90)90024-l.