VASOCONSTRICTION IN RAT ISOLATED MESENTERY AND SMALL-INTESTINE IN RESPONSE TO VARIOUS ACTIVATORS OF PROTEIN-KINASE-C

The vasculature of rat isolated mesentery and small intestine was perf used with a gelatin-containing physiological salt solution (GPSS). Whe n 5-hydroxytryptamine (5HT, 1 x 10(-4) M), or the calcium ionophore A2 3187 (1 x 10(-4) M), or 12-deoxyphorbol 13-phenylacetate (DOPPA, 1 x 1 0(-6) M), or 12-deoxyphorbol 13-phenylacetate 20-acetate (DOPPAA, 1 x 10(-6) M) or thymeleatoxin (TMX, 1 x 10(-6) M) was added to the GPSS f or 5 min there was a gradual rise in perfusion pressure, whereas resin iferatoxin (RFX, 1 x 10(-6) M) was without effect. Pre-treatment of th e tissue with the protein kinase C (PKC) inhibitor Ro 31-8220 (1 x 10( -6) M) significantly reduced the rise in perfusion pressure in respons e to 5HT, DOPPA, DOPPAA and TMX, but not that to A23187. Platelet-acti vating factor (PAF, 5 x 10(-6) M) caused an almost immediate but trans ient rise in perfusion pressure, followed by a more gradual rise, neit her response being blocked by Ro 31-8220. When blood vessels of the me sentery alone were perfused with gelatin-free PSS, PAF caused a transi ent rise in perfusion pressure, but with no subsequent gradual rise ov er 5 min. After Ca2+-depletion this transient response was also absent . In contrast, when blood vessels were perfused with gelatin-free PSS, DOPPA and TMX still caused gradual rises in perfusion pressure, which were totally abolished by Ro 31-8220. TMX had no effect at all when t he tissue was depleted of Ca2+, whereas the response to DOPPA was only partially reduced. Phenylephrine (PE, 1 x 10(-6) M) produced a fairly rapid but nonsustained rise in perfusion pressure, which was reduced by Ro 31-8220, and more or less abolished by Ca2+-depletion. It is sug gested that the presser response to DOPPA involved activation of both Ca2+-dependent and Ca2+-independent PKC isoenzymes. TMX and PE, howeve r, appear to activate only a Ca2+-dependent isoenzyme.