Yangambin, a Lignan Obtained from Ocotea duckei, Differentiates Putative PAF Receptor Subtypes in the Gastrointestinal Tract of Rats

Abstract

We investigated the presence of PAF receptor subtypes in the tissues of the gastrointestinal tract, airways, blood vessels and in murine macrophages. For this purpose we have used a competitive PAF receptor antagonist, yangambin (YAN), extracted from the Brazilian plant “louro de cheiro” (Ocotea duckei Vattimo). Rat duodenum, jejunum, ileum, colon, stomach fundus, trachea and bronchia were removed and 1.5 - 2 cm muscle segments from those regions were mounted in a 10 ml organ bath with aerated physiological solution at 37 °C. PAF evoked a contraction of the rat jejunum, ileum, colon and stomach fundus. The contraction was slow and resistant to wash and was followed by desensitization to further doses of PAF. Contractions induced by PAF (10^-6 M) were inhibited by YAN (10^-7 to M - 2 × 10^-5 M) and WEB 2086 (10^-6 m to M^-5 M) in rat jejunum, ileum and colon but not in the stomach fundus. In the rat stomach fundus only WEB 2086 (5 × 10^-6 M) was able to block PAF-induced contraction. The contractions induced by acetylcholine, histamine, 5-hydroxytryptamine and vasopressin were not inhibited by prior administration of YAN. Yangambin also significantly inhibited PAF-induced vascular permeability in rat duodenum, jejunum, ileum, colon, and mesentery. Yangambin significantly inhibited PAF-induced lipid body formation in mice peritoneal macrophages. We suggest that YAN is a selective PAF antagonist which is able to discriminate putative PAF receptors subtypes present in the stomach fundus.

Key words

Yangambin - Ocotea duckei - Lauraceae - PAF - PAF-receptor subtypes - natural product

References

• 1 Braquet  P,, Touqui  L,, Shen  T Y,, Vargaftig  B B.. Pharmacol. Rev.. 1987;;  39 97-133
• 2 Bozza  P T,, Payne  J L,, Goulet  J L,, Weller  P F.. J. Exp. Med.. 1996;;  183 1515-25
• 3 Stewart  A G,, Phillips  W A.. Br. J. Pharmacol.. 1989;;  98 141-8
• 4 Honda  Z,, Nakamura  M,, Miki  I,, Minami  M,, Watanabe  T,, Seyama  Y,, Okado  H,, Toh  H,, Ito  K,, Miyamoto  T,, Shimizu  T.. Nature. 1991;;  349 342-6
• 5 Nakamura  M,, Honda  Z,, Izumi  T,, Sakanka  C,, Mutoh  H,, Minami  M,, Bito  H,, Seyama  Y,, Matsumoto  T,, Noma  M,, Shimizu  T.. J. Biol. Chem.. 1991;;  266 20400-5
• 6 Shen  T Y,, Hwang  S B,, Chang  M N,, Doebber  T W,, Lam  M HT,, Wu  M S,, Wang  X,, Han  G Q,, Li  R Z.. Biochemistry. 1985;;  82 672-6
• 7 Biftu  T,, Stevenson  R.. Phytother. Res.. 1987;  1 97-106
• 8 Castro-Faria-Neto  H C,, Bozza  P T,, Cruz  H N,, Silva  C LM,, Violante  F A,, Barbosa-Filho  J M,, Thomas  G M,, Martins  M A,, Tibiriça  E V,, Noel  F,, Cordeiro  R SB.. Planta Med.. 1995;;  61 101-5
• 9 Castro-Faria-Neto  H C,, Araújo  C V,, Moreira  S,, Bozza  P T,, Thomas  G M,, Barbosa-Filho  J M,, Cordeiro  R SB,, Tibiriça  E V.. Planta Med.. 1995;;  61 106-12
• 10 Herbert  J M,, Castro-Faria-Neto  H C,, Barbosa-Filho  J M,, Cordeiro  R SB,, Tibiriça  E.. J. Lipid Mediators Cell Signalling. 1997;;  17 1-14
• 11 Lambrecht  G,, Parnham  M J.. Br. J. Pharmac.. 1986;;  87 287-9
• 12 Jancar  S,, Sirois  M G,, Carrier  J,, Braquet  P,, Sirois  P.. Inflammation. 1991;;  15 (5) 347-54
• 13 De Queiroz Paulo  M,, Kaplan  M AC,, Laprévote  O,, Roblot  F,, Hocquemiller  R,, Cavé  A.. Fitoterapia. 1991;;  LXII 150-2
• 14 Corfield  D R,, Webber  S E,, Widdicombe  J G.. Br. J. Pharmacol.. 1991;;  103 1740-44
• 15 Tokumura  A,, Furkuzawa  K,, Tsukatani  H.. J. Pharm. Pharmacol.. 1984;;  36 210-2
• 16 Levy  J V.. Biochem. Bioph. Res. Commun.. 1987;;  146 855-60
• 17 Hwang  S B.. J. Biol. Chem.. 1988;;  263 3225-33
• 18 O'Donnell  S R,, Barnett  C JK.. Br. J. Pharmacol.. 1988;;  94 437-42
• 19 Thureson-Klein  A,, Hedqvist  A,, Öhlen  A,, Raud  J,, Lindbom  L.. Pathol. Immunopathol. Res.. 1987;;  6 190-206
• 20 Bozza  P T,, Yu  W,, Penrose  J F,, Morgan  E S,, Dvorak  A M,, Weller  P F.. J. Exp. Med.. 1997;;  186 909-20