The importance of Ca2+-mediated phospholipase A2 activation for stimulus-evoked PGE2-release from rabbit splenic capsular strips.
Rabbit splenic capsular strips released PGE2 when contracted by noradrenaline. Contraction as well as PGE2-release were Ca2+-dependent. In the presence of Ca2+ the ionophore A 23187 induced a long lasting contraction and a vigorous PGE2-release. In Ca2+-free medium the ionophore was ineffective. Introduction of Ca2+ to splenic strips preincubated with the ionophore in the absence of Ca2+ reinstalled contracture and PGE2-release. The PGE2-release induced induced by the PG-precursor arachidonic acid was Ca2+-independent. Addition of phospholipase A to splenic strips elicited a strong PGE2-release. These results indicate, that the first step of stimulus evoked PG-release is the Ca2+-mediated activation of phospholipase A2. This enzyme liberates from membrane bound phospholipids C-20-fatty acids, which then serve as substrates for the PG-synthetizing enzymes. Therefore the rate limiting step in stimulus-evoked PG-release seems to be rather the phospholipase A2 activity than the state of activation of one of the PG-synthetizing enzymes.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011458:Prostaglandins E / Q000378:metabolism*; D011817:Rabbits; D013154:Spleen / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D011458:Prostaglandins E; D000001:Calcimycin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium; D009638:Norepinephrine