title: The phosphatidate-phosphoinositide cycle: an intracellular messenger system in the action of hormones and neurotransmitters.
abstract: Many hormones and neurotransmitters provoke rapid and striking changes in the metabolism of phospholipids in the phosphatidate-inositide cycle. These changes appear to occur before and after the generation of other accepted "second messengers" (e.g., Ca++ and cAMP), and seem to be important intracellular effector substances for the elicitation of biological effects. The two major mechanisms for perturbing the phosphatidate-inositide cycle are phosphatidylinositol hydrolysis and de novo phosphatidate-inositide synthesis. Phosphatidylinositol hydrolysis occurs in the action of all agents which operate via Ca++ and appears to be provoked both by Ca++-dependent and Ca++-independent mechanisms. Ca++-independent phosphatidylinositol hydrolysis may be triggered directly by receptor activation and may control Ca++ release or entry into the cytosol. Ca++-dependent phosphatidylinositol hydrolysis may be important for further changes in cellular Ca++ distribution and membrane fusion during exocytosis. The de novo phosphatidate-inositide synthesis effect has been observed in the action of most steroidogenic agents (ACTH, luteinizing hormone, angiotensin II, K+, serotonin), parathyroid hormone and insulin. The de novo effect is inhibited by cycloheximide, requires Ca++, and appears to serve as a post-second messenger mechanism to alter membrane structure and the function of membrane associated substances. Considerable evidence suggests that the de novo effect is important in the control of steroidogenesis by the above-mentioned agents; it may also be important in the action of insulin in adipose tissue.
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D006728:Hormones / Q000502:physiology*; D006801:Humans; D006868:Hydrolysis; D018377:Neurotransmitter Agents / Q000502:physiology*; D010712:Phosphatidic Acids / Q000096:biosynthesis*; D010716:Phosphatidylinositols / Q000096:biosynthesis*
chemical_list: D006728:Hormones; D018377:Neurotransmitter Agents; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D002118:Calcium