The effects of colchicine on prostaglandin I2 and thromboxane A2 biosynthesis in the rat dental pulp.
Pulp tissues isolated from rats treated with either colchicine (0.5, 0.75 or 1.0 mg/kg) or beta-lumicolchicine (1.0 mg/kg) for 24 h were incubated in Tyrode buffer. Prostaglandin (PG) I2 and thromboxane (TX) A2 released into the medium were determined by radioimmunoassay as their stable metabolites, 6-keto-PGF1 alpha and TXB2, respectively. Colchicine generally enhanced PGI2 and TXA2 production concomitantly with hypocalcaemia, except that 0.5 mg/kg dosage had no significant effects. This enhancement was greater in PGI2 than in TXA2 synthesis, but was not observed in PGI2 release from aortic tissue. beta-Lumicolchicine (1.0 mg/kg) had no effect on PG and TX synthesis, nor on serum calcium. Kinetic studies revealed that after a lag period of more than 12 h, 1.0 mg/kg colchicine caused a progressive increase in the production of PGI2 and TXA2, which reached a maximum at 24 h and decreased thereafter gradually to the basal level within 168 h (7 days). In contrast, the hypocalcaemic effect of colchicine appeared rapidly, reached a maximum within 3 h and gradually recovered to the control level within 7 days. Colchicine at concentrations of 1-1000 microM had no stimulatory effect on PGI2 and TXA2 biosynthesis when incubated in vitro with isolated pulp tissues; it was inhibitory at higher concentrations. The enhancing effect of colchicine treatment on PGI2 and TXA2 production in dental pulp tissue may be caused indirectly by interaction of this agent with microtubules, but the precise mechanisms are unclear. Thus, a drug known to affect dentinogenesis modifies arachidonic-acid metabolism in dental pulp.
Hirafuji
M
M
Department of Pharmacology, Tohoku University School of Dentistry, Sendai, Japan.
Ogura
Y
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology*; D003782:Dental Pulp / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000096:biosynthesis*; D007700:Kinetics; D008162:Lumicolchicines / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013928:Thromboxane A2 / Q000096:biosynthesis*
D008162:Lumicolchicines; C042109:lumicolchicine; D013928:Thromboxane A2; D011464:Epoprostenol; D003078:Colchicine; D002118:Calcium