The mechanism of phosphate exchange in phosphatidic acid in response to acetylcholine.

Acetylcholine stimulates the exchange of phosphate in phosphatidic acid in guinea pig brain cortex slices (1) and in cytoplasmic particulate fractions of brain which are undergoing oxidative phosphorylation (2). In this paper the reactions involved in the acetylcholine effect in brain microsomal preparations have been investigated. The data presented here indicate that in brain microsomes phosphatidic acid may be formed either from oc-glycerophosphate by the Kornberg and Pricer mechanism (3) or from adenosine triphosphate and diglyceride (4). Acetylcholine does not increase the formation of phosphatidic acid from a-glycerophosphate; it does increase the formation of phosphatidic acid from ATP. Atropine blocks the acetylcholine effect. The effect does not occur after the microsomes have been frozen, or under conditions of hypotonicity, or after treatment with deoxycholate. The ability to respond to acetylcholine appears therefore to be dependent on the structural integrity of the membranous fragments of the microsomal preparations. The turnover of phosphatidic acid and phosphoinositide in glands is associated with secretory activity (5-8). The possible significance of the exchange of phosphate in phosphatidic acid, catalyzed by diglyceride kinase and phosphatidic acid phosphatase, in the secretory process is briefly discussed.