The effects of noradrenaline and adenosine 5'-triphosphate on polyphosphoinositide and phosphatidylcholine hydrolysis in arterial smooth muscle.
1. The effects of noradrenaline and alpha,beta,methylene adenosine 5'-triphosphate (alpha,beta,methylene ATP) on polyphosphoinositide metabolism, phosphatidylcholine hydrolysis and contraction in rabbit saphenous arteries were investigated. The effect of noradrenaline upon polyphosphoinositide metabolism was also investigated in the rat tail artery. 2. Noradrenaline (10(-7)-10(-4) M) evoked a concentration-dependent increase in total inositol phosphate accumulation in the rat tail but not in the rabbit saphenous artery. Propranolol (3 x 10(-6) M) did not alter this result in the rabbit saphenous artery. In addition, alpha,beta,methylene ATP (10(-6) M) significantly increased total inositol phosphate accumulation in the rabbit saphenous artery, while potassium chloride (8 x 10(-2) M) was ineffective. 3. Phorbol 1,2-myristate 1,3-acetate (3 x 10(-8) M) enhanced noradrenaline (10(-2)-10(-4) M)-evoked contractions in rabbit saphenous artery. The contractile responses to potassium chloride (1- 16 x 10(-2) M) in tissues treated with 6-hydroxydopamine (5 x 10(-4) M), in vitro, were unaffected by these concentrations of the phorbol ester. 4. Noradrenaline (10(-6)-10(-4) M) evoked a concentration-dependent increase in the levels of choline and choline phosphate, but not in those of glycerophosphocholine, in the rabbit saphenous artery. Choline levels increased significantly over the first 15-30 s then declined to control levels within 2 min of addition of noradrenaline (10(-5) M). A smaller initial rise in choline phosphate levels (15-30 s) was followed by a larger secondary rise at 2-4 min.5. alpha, beta, methylene ATP (10-1_ 0-4 M) also evoked a concentration-dependent increase in the levels of both choline and choline phosphate, but not those of glycerophosphocholine, in the rabbit saphenous artery. alpha, beta, methylene ATP (10-4 M) significantly increased levels of both of these products within the first 15-30 s of addition of the drug; these levels reached a stable plateau 1 min after addition.6. The maximum accumulation of choline or choline phosphate evoked by either noradrenaline or alpha, beta, methylene ATP, acting alone or in combination, was not significantly different. No evidence of synergism between noradrenaline and alpha, beta, methylene ATP was observed.7. This study demonstrates that each of the co-transmitters in the rabbit saphenous artery, noradrenaline and adenosine 5'-triphosphate (ATP), promote phosphatidylcholine hydrolysis. Noradrenaline seems to rely on phosphatidylcholine hydrolysis to mediate its contractile effects, whilst ATP promotes both polyphosphoinositide and phosphatidylcholine metabolism suggesting that multiple signal-transduction mechanisms are involved in stimulus-contraction coupling in this artery.
Nally
J E
JE
Department of Pharmacology, University of Glasgow.
Muir
T C
TC
Guild
S B
SB
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002794:Choline / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010767:Phosphorylcholine / Q000032:analysis; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014316:Tritium
D010703:Phorbol Esters; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D014316:Tritium; D010767:Phosphorylcholine; D000255:Adenosine Triphosphate; D002794:Choline; D009638:Norepinephrine