Vasoconstriction in rat isolated mesentery and small intestine in response to various activators of protein kinase C

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Abstract
The vasculature of rat isolated mesentery and small intestine was perfused with a gelatin-containing physiological salt solution (GPSS). When 5-hydroxytryptamine (5HT, 1×10−4 M), or the calcium ionophore A23187 (1×10−4 M), or 12-deoxyphorbol 13-phenylacetate (DOPPA, 1×10−6 M), or 12-deoxyphorbol 13-phenylacetate 20-acetate (DOPPAA, 1×10−6 M) or thymeleatoxin (TMX, 1×10−6 M) was added to the GPSS for 5 min there was a gradual rise in perfusion pressure, whereas resiniferatoxin (RFX, 1×10−6 M) was without effect. Pre-treatment of the tissue with the protein kinase C (PKC) inhibitor Ro 31-8220 (1×10−6 M) significantly reduced the rise in perfusion pressure in response to 5HT, DOPPA, DOPPAA and TMX, but not that to A23187. Platelet-activating factor (PAF, 5×10−6 M) caused an almost immediate but transient rise in perfusion pressure, followed by a more gradual rise, neither response being blocked by Ro 31-8220. When blood vessels of the mesentery alone were perfused with gelatin-free PSS, PAF caused a transient rise in perfusion pressure, but with no subsequent gradual rise over 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 the tissue was depleted of Ca2+, whereas the response to DOPPA was only partially reduced. Phenylephrine (PE, 1×10−6 M) produced a fairly rapid but non-sustained rise in perfusion pressure, which was reduced by Ro 31-8220, and more or less abolished by Ca2+-depletion. It is suggested that the pressor response to DOPPA involved activation of both Ca2+-dependent and Ca2+-independent PKC isoenzymes. TMX and PE, however, appear to activate only a Ca2+-dependent isoenzyme.