The substance P fragment SP-(7-11) increases prostaglandin E2, intracellular Ca2+ and collagenase production in bovine articular chondrocytes.
Substance P (SP) is found in increased concentrations in inflamed joints and is believed to play a role in joint pathology. Culture of bovine articular chondrocytes with SP or with the related mammalian tachykinins neurokinin A or B (NKA or NKB) produced no effect on prostaglandin E2 (PGE2) or collagenase production. However, the C-terminal fragment of SP, SP-(7-11), increased PGE2 and collagenase production at concentrations greater than 1 microM. The N-terminal fragments SP-(1-4) and SP-(1-6) had no effect on PGE2 or collagenase production. In addition, SP-(7-11), but not intact SP, SP-(1-4), SP-(1-6), SP-(8-11) or SP-(9-11), nor the tachykinins NKA and NKB, caused an increase in the intracellular calcium concentration as measured by the fluorescent dye Fura-2. The maximal change in intra-cellular calcium induced by 10 microM SP-(7-11) was 140 +/- 30 nM. We postulate that cleavage of SP by neutral endopeptidases which are present in the synovial fluid and which yield SP-(7-11) may be of biological importance in chondrocyte-mediated cartilage pathology.
Halliday
D A
DA
Department of Medicine, University of Adelaide, South Australia.
McNeil
J D
JD
Betts
W H
WH
Scicchitano
R
R
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002358:Cartilage, Articular / Q000201:enzymology / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D017364:Collagenases / Q000096:biosynthesis* / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology*; D013373:Substance P / Q000737:chemistry / Q000502:physiology*
D010446:Peptide Fragments; D013373:Substance P; C061335:substance P (7-11); D017364:Collagenases; D015232:Dinoprostone; D002118:Calcium