CHANGES IN PHOSPHOLIPID METABOLISM ON STIMULATION OF PROTEIN SECRETION IN PANCREAS SLICES.
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Biomedical subjects
Publications and source records attributed to M R HOKIN.
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Incubation of slices of the salt gland of the albatross with acetylcholine, which is the physiological secretogogue for this tissue, led to a 13-fold increase in the rate of incorporation of P(32) into phosphatidic acid and a 3-fold increase in the incorporation of P(32) and inositol-2-H(3) into phosphoinositide. The incorporation of P(32) into phosphatidyl choline and phosphatidyl ethanolamine was increased relatively slightly or not at all. Respiration was doubled. The "phospholipid effect" occurred in the microsome fraction, which is known to contain fragments of the endoplasmic reticulum. The enzymes, diglyceride kinase and phosphatidic acid phosphatase, which catalyze the stimulated turnover of phosphatidic acid in brain cortex, were also found in highest concentration in the microsome fraction. The phosphatides which respond to acetylcholine are bound to protein in the membrane. On the basis of these findings it appears that phosphatidic acid and possibly phosphoinositide participate in sodium transport. A scheme, termed the phosphatidic acid cycle, is presented as a working hypothesis, in which the turnover of phosphatidic acid in the membrane, catalyzed by diglyceride kinase and phosphatidic acid phosphatase, functions as a sodium pump.
The effect of acetylcholine on the incorporation of P(32) into the individual phosphatides in slices of various structures of the nervous system has been studied. There was a marked stimulation of P(32) incorporation into phosphoinositide and phosphatidic acid, but not into phosphatidyl choline and phosphatidyl ethanolamine, in the cat stellate and celiac ganglia in vitro. Acetylcholine stimulated P(32) incorporation into certain phosphatides, primarily phosphoinositide and phosphatidic acid, in several structures of the cat and guinea pig brain; there was little or no effect of acetylcholine on phosphatide turnover in the inferior corpora quadrigsemina and cerebellar cortex. The suggestion is made that the phospholipid effect can best be explained as being concerned with the active transport of sodium ions out of the cell across the postsynaptic membrane of cholinergic neurons in response to acetylcholine.
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