ROLE OF PROTEIN KINASE C IN THE REGULATION OF PUMPING ACTIVITY IN BOVINE MESENTERIC LYMPHATIC VESSELS

Abstract

We investigated the role of protein kinase C (PKC) in regulating the lymphatic myogenicresponse. Bovine mesenteric lymphatics were suspended in an organ bath with inflow andoutflow ends cannulated. Input was provided from a reservoir filled with Krebs solution. ThePKC activator phorbol 12-myristate 13-acetate (PMA) inhibited pumping significantly whethertested at a fixed pressure or as pressures were raised in 2 cm H2O increments (50% inhibitionachieved at 4.6 X 10-8M). The inactive phorbol ester (4-"-PMA) had no effect. The specific PKCinhibitors calphostin (10-9 to 10-7M) or chelerythrine (10-8 to 10-6M) had no significant effect onpumping. However, chelerythrine (10-6M) was capable of reversing the inhibitory effects of PMA(5 X 10-8M). PKC activation is believed to inhibit nitric oxide (NO) production in some bloodvessels, and previous work from our laboratory has demonstrated that NO is important infacilitating pumping activity in bovine lymphatics. We observed that sodium nitroprusside (sNP,10-7M) or L-arginine (10-4M), reversed the depressor effects of PMA. These results suggest thatPKC may not be involved in regulating the vessel's contractile response to pressure-inducedstretch. However, the data with PMA suggest that these ducts contain PKC. PKC activationdepresses lymphatic pumping and this effect may be mediated in part, by inhibition of