Phorbol 12,13-Diacetate-Induced Contraction of the Canine Basilar Artery: Role of Protein Kinase C

Abstract

The pharmacological and biochemical mechanisms of contractile responses to the protein kinase C (PKC) activator phorbol-12, 13-diacetate (PDA) were investigated in canine basilar arteries, In the normal medium, PDA elicited a strong, dose-related, and slow-developing sustained contraction, Among the constrictors examined, including serotonin, prostaglandin F_2α and endothelin, only PDA yielded contractions in a 2 Ca²⁺ -free medium, In both media, the PDA-induced contractions were virtually inhibited by either staurosporine, H-7, or quinacrine, while neither neurotransmitter blockades nor R24571 (calmidazolium) exerted significant effects, In addition, it was shown that 8-bromocyclic GMP, but not 8-bromocyclic AMP, markedly curtailed the PDA-induced contractions, Biochemical analysis, furthermore, showed that PDA induced increased phosphorylations of 27- and 96-kDa and proteins other than the myosin light chain (MLC) 20-kDa protein, Thus, the present results open up a novel mechanism of sustained cerebral artery contractions, where PKC activation rather than Ca²⁺/calmodulin/MLC system plays a key role that is regulated both by phospholipase A 2 and by cyclic GMP.

Keywords

Canine basilar artery Contractile protein Contraction Cyclic nucleotides Phorbol 12,13-diacetate Protein kinase C

References

Adelstein

R.S.

Conti

M.A.

Pato

M.D.

(1980) Regulation of myosin light chain kinase by reversible phosphorylation and calcium-calmodulin. Ann NY Acad Sci 356:142–150.

Aksoy

M.O.

Mras

Kamm

K.E.

Murphy

R.A.

(1983) Ca2+, cAMP, and changes in myosin phosphorylation during contraction of smooth muscle. Am J Physiol 245:c255–c270.

Baraban

J.M.

Gould

R.J.

Peroutka

S.J.

Snyder

S.H.

(1985) Phorbol ester effects on neurotransmission: Interaction with neurotransmitters and calcium in smooth muscle. Proc Natl Acad Sci USA 82:604–607.

Bolton

T.B.

(1979) Mechanisms of action of transmitters and other substances on smooth muscle. Physiol Rev 59:606–718.

Chatterjee

Foster

(1987) Activation of protein kinase C and contraction in skinned vascular smooth muscle. Prog Clin Biol Res 245:219–231.

Chatterjee

Murphy

R.A.

(1983) Calcium-dependent stress maintenance without myosin phosphorylation in skinned smooth muscle. Science 221:464––466.

Chiu

A.T.

Bozarth

J.M.

Forsythe

M.S.

Timmermans

P.B.M.W.M.

(1987) Ca++ utilization in the constriction of rat aorta to stimulation of protein kinase C by phorbol dibutyrate. J Pharmacol Exp Ther 242:934–939.

Danthuluri

N.R.

Deth

R.C.

(1984) Phorbol ester-induced contraction of arterial smooth muscle and inhibition of α-adrenergic response. Biochem Biophy Res Commun 125:1103–1109.

Draznin

M.B.

Rapoport

R.M.

Martinez

G.A.

Murad

(1983) Myosin light chain dephosphorylation in intact rat thoracic aorta treated with sodium nitroprusside: Role of cyclic GMP. Clin Res 31:466A.

10.

Draznin

M.B.

Rapoport

R.M.

Murad

(1986) Myosin light chain phosphorylation in contraction and relaxation of intact rat thoracic aorta. Int J Biochem 18:917–928.

11.

Edgar

A.D.

Freysz

(1982) Phospholipase activities of rat brain. Cytosol occurrence of phospholipase C activity with phosphatidylcholine. Biochim Biophy s Acta 711:224–228.

12.

Edwards

J.C.

Ignarro

L.J.

Hyman

A.L.

Kadowitz

P.J.

(1984) Relaxation of intrapulmonary artery and vein by nitrogen oxide-containing vasodilators and cyclic GMP. J Pharmacol Exp Ther 228:33–42.

13.

Farooqui

A.A.

Farooqui

Yates

A.J.

Horrocks

L.A.

(1988) Regulation of protein kinase C activity by various lipids. Neurochem Res 13:499–511.

14.

Flower

R.J.

(1974) Drugs which inhibit prostaglandin biosynthesis. Pharmacol Rev 26:33–67.

15.

Forder

Scriabine

Rasmussen

(1985) Plasma membrane calcium flux, protein kinase C activation and smooth muscle contraction. J Pharmacol Exp Ther 235:267–273.

16.

Gietzen

Wüthrich

Bader

(1981) R24571: A new powerful inhibitor of red blood cell Ca++-transport ATPase and of calmodulin-regulated functions. Biochem Biophy s Res Commun 101:418–425.

17.

Gleason

M.M.

Flaim

S.F.

(1986) Phorbol ester contracts rabbit thoracic aorta by increasing intracellular calcium and by activating calcium influx. Biochem Biophys Res Commun 138:1362–1369.

18.

Griendling

K.K.

Rittenhouse

S.E.

Brock

T.A.

Ekstein

L.S.

Gim-Brone

M.A.

Jr Alexander

R.W.

(1986) Sustained diacylglycerol formation from inositol phospholipids in angiotensin II-stimulated vascular smooth muscle cells. J Biol Chem 261:5901–5906.

19.

Gruetter

C.A.

Gruetter

D.Y.

Lyon

J.E.

Kadowitz

P.J.

Ignarro

L.J.

(1981) Relationship between cyclic guanosine 3′:5′-monophosphate formation and relaxation of coronary arterial smooth muscle by glyceryl trinitrate, nitroprusside, nitrite and nitric oxide: Effects of methylene blue and methemoglobin. J Pharmacol Exp Ther 219:181–186.

20.

Hansson

Serhan

C.N.

Haeggström

Ingelman-Sundberg

Samuelsson

(1986) Activation of protein kinase C by lipoxin A and other eicosanoids: Intracellular action of oxygenation products of arachidonic acid. Biochem Biophys Res Commun 134:1215–1222.

21.

Huang

K-P

, (1989) The mechanism of protein kinase C activation. Trends Neurosci 12:425–432.

22.

Ignarro

L.J.

Lippton

Edwards

J.C.

Baricos

W.H.

Hyman

A.L.

Kadowitz

P.J.

Gruetter

C.A.

(1981) Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: Evidence for the involvement of s-nitrosothiols as active intermediates. J Pharmacol Exp Ther 218:739–749.

23.

Ikebe

Inagaki

Kanamaru

Hidaka

(1985) Phosphorylation of smooth muscle myosin light chain kinase by Ca2+ -activated, phospholipid-dependent protein kinase. J Biol Chem 260:4547–4550.

24.

Kawamoto

Hidaka

(1984) 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine (H-7) is a selective inhibitor of protein kinase C in rabbit platelets. Biochem Biophys Res Commun 125:258–264.

25.

Khalil

R.A.

Van Breemen

(1988) Sustained contraction of vascular smooth muscle: Calcium influx or C-kinase activation? J Pharmacol Exp Ther 244:537–542.

26.

Koide

Noda

Hata

Sugioka

Kobayashi

Nakano

(1981) Contraction of the canine basilar artery following linoleic, arachidonic, 13-hydroperoxylinoleic, or 15-hydroperoxyarachidonic acid (41294). Proc Soc Exp Biol Med 168:399–402.

27.

Koide

Neichi

Takato

Matsushita

Sugioka

Nakano

Hata

(1982) Possible mechanisms of 15-hydroperoxyarachidonic acid-induced contraction of the canine basilar artery in vitro. J Pharmacol Exp Ther 221:481–488.

28.

Kroeger

E.A.

Teo

T.S.

Wang

J.H.

(1977) Relaxants, cyclic AMP and calcium metabolism in smooth muscle. In: The Biochemistry of Smooth Muscle ( Stephens

N.L.

, eds), Baltimore, University Park Press, pp 641–652.

29.

Malenka

R.C.

Madison

D.V.

Nicoll

R.A.

(1986) Potentiation of synaptic transmission in the hippocampus by phorbol esters. Nature 321:175–177.

30.

Markovac

Goldstein

G.W.

(1988) Picomolar concentrations of lead stimulate brain protein kinase C. Nature 334:71–73.

31.

Markus

H.B.

Ball

E.G.

(1969) Inhibition of lipolytic processes in rat adipose tissue by antimalarial drugs. Biochim Biophys Acta 187:486–491.

32.

McPhail

L.C.

Clayton

C.C.

Snyderman

(1984) A potential second messenger role for unsaturated fatty acid: Activation of Ca2+ -dependent protein kinase. Science 224:622–625.

33.

Murphy

R.A.

Aksoy

M.O.

Dillon

P.F.

Gerthoffer

W.T.

Kamm

K.E.

(1983) The role of myosin light chain phosphorylation in regulation of the cross-bridge cycle. Fed Proc 42:51–56.

34.

Nishizuka

(1984) The role of protein kinase C in cell surface signal transduction and tumor promotion. Nature 308:693–698.

35.

Nishizuka

(1986) Studies and perspectives of protein kinase C. Science 233:305–312.

36.

Nishizuka

(1988) The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature 334:661–665.

37.

Nishizuka

(1989) Studies and prospectives of the protein kinase C family for cellular regulation. Cancer 63:1892–1903.

38.

Oishi

Raynor

R.L.

Charp

P.A.

Kuo

J.F.

(1988) Regulation of protein kinase C by lysophospholipids: Potential role in signal transduction. J Biol Chem 263:6865–6871.

39.

Park

Rasmussen

(1985) Activation of tracheal smooth muscle contraction: Synergism between Ca2+ and activators of protein kinase C. Proc Natl Acad Sci USA 82:8835–8839.

40.

Park

Rasmussen

(1986) Carbachol-induced protein phosphorylation changes in bovine tracheal smooth muscle. J Biol Chem 261:15734–15739.

41.

Pritchard

Moody

Caldesmon

(1986) A calmodulin-binding actin-regulatory protein. Cell Calcium 7:309–328.

42.

Rasmussen

Forder

Kojima

Scriabine

(1984) TPA-induced contraction of isolated rabbit vascular smooth muscle. Biochem Biophys Res Commun 122:776–784.

43.

Rasmussen

Takuwa

Park

(1987) Protein kinase C in the regulation of smooth muscle contraction. FASEB J 1:177–185.

44.

Rembold

C.M.

Murphy

R.A.

(1986) Myoplasmic calcium, myosin, phosphorylation, and regulation of the cross bridge cycling in swine arterial smooth muscle. Circ Res 58:803–815.

45.

Stephens

N.L.

Kroeger

E.A.

(1981) Calcium sequestration and relaxation of vascular smooth muscle. In: Vasodilatation ( Vanhoutte

P.M.

Leusen

, eds), New York, Raven Press, pp 367–380.

46.

Summerville

L.E.

Hartshorne

D.J.

(1986) Intracellular calcium and smooth muscle contraction. Cell Calcium 7:353–364.

47.

Takuwa

Rasmussen

(1986) Carbachol induces a rapid and sustained hydrolysis of polyphosphoinositides in bovine tracheal muscle. J Biol Chem 261:14670–14675.

48.

Takuwa

Kelley

Takuwa

Rasmussen

(1988) Protein phosphorylation changes in bovine carotid artery smooth muscle during contraction and relaxation. Mol Cell Endocrinol 60:71–86.

49.

Tamaoki

Nomoto

Takahashi

Kato

Morimoto

Tomita

(1986) Staurosporine, a potent inhibitor of phospholipid/Ca++ dependent protein kinase. Biochem Biophys Res Commun 135:397–402.

50.

Ueda

Greengard

(1977) Adenosine 3′:5′-monophosphate-regulated phosphoprotein system of neuronal membranes. J Biol Chem 252:5155–5163.

51.

Van Breemen

Aaronson

Loutzenhiser

(1979) Na-Ca interactions in mammalian smooth muscle. Pharmacol Rev 30:167–208.

52.

Waldman

S.A.

Murad

(1987) Cyclic GMP synthesis and function. Pharmacol Rev 39:163–196.

53.

Webb

R.C.

Bhala

R.C.

(1976) Calcium sequestration by subcellular fractions isolated from vascular smooth muscle: Effects of cyclic nucleotides and prostaglandins. J Mol Cell Cardiol 8:145–157.

54.

(1981) Calcium-activated, phospholipid-dependent protein kinase in smooth muscle and its possible relationship to phosphatidylinositol turnover. Kobe J Med Sci 27:225–237.