Sapintoxin A and Phorbol 12, 13-Dibutyrate: Two Phorbol Derivatives with Contrasting Effects on Rat Blood Vessel Permeability In-vitro

Abstract

Abstract Rat isolated small intestine and mesentery were perfused with a gelatin-containing physiological salt solution, and microvascular permeability in the villi was assessed using colloidal carbon as a marker to assess the effect of sapintoxin A in this experimental situation, and to compare it with phorbol 12, 13-dibutyrate. Sapintoxin A (1, 0·25, 0·1 μm) had no effect on colloidal carbon leakage compared with control values, but significantly increased perfusion pressure. Phorbol 12, 13-dibutyrate (1 μm) significantly increased both colloidal carbon leakage and perfusion pressure. Pretreatment with the protein kinase C inhibitor Ro 31–8220 (1 μm) significantly increased colloidal carbon leakage in the presence of sapintoxin A, but significantly decreased the phorbol 12, 13-dibutyrate-induced leakage of colloidal carbon. Pretreatment with indomethacin (1 μm) significantly increased colloidal carbon leakage in response to sapintoxin A, but did not affect the response to phorbol 12, 13-dibutyrate. Increases in perfusion pressure caused by sapintoxin A (0·25 μm) and phorbol 12, 13-dibutyrate (1 μm) were reduced by Ro 31–8220, but neither pressor response was affected by indomethacin. Lower concentrations of phorbol 12, 13-dibutyrate (0·25, 0·1 μm) had no effect on colloidal carbon leakage. However, there was a significant increase in perfusion pressure in response to 0·25 μm but not to 0·1 μm phorbol 12, 13-dibutyrate. When rat mesentery alone was perfused using gelatin-free physiological salt solution, sapintoxin A (1 μm) had no effect on perfusion pressure, whereas phorbol 12, 13-dibutyrate (1 μm) caused a significant increase over a 15-min period, which was completely abolished by pretreatment with Ro 31–8220. It may be concluded that the permeability-increasing effects of phorbol 12, 13-dibutyrate are dependent on protein kinase C activation.