Purinergic vs peptidergic stimulation of lipolysis and prostaglandin generation in the perfused rabbit kidney

Intact perfused rabbit kidney contains three different systems for generation of arachidonate oxygenated products. Each of these systems is associated with its specific type of activating agonist; the agonists are the vasoactive peptide hormones bradykinin and angiotensin II, the adenine nucleotides ATP and ADP, and exogenous arachidonic acid. The three systems are clearly distinguished by several biochemical parameters which include the type of lipolysis induced and the extent of coupling between the hydrolyzed arachidonic and its conversion to specific oxygenated products. The highest degree of selectivity in the lipolytic process and in the coupling to PGE₂ generation is seen following stimulation with bradykinin or angiotensin II. These hormones induce the hydrolysis of only arachidonic and PGE₂ is the major product. Furthermore, arachidonate hydrolysis is from a unique lipid pool which is characterized by a slow turnover of arachidonic. The entire process of lipolysis and prostaglandin E₂ synthesis is terminated within 1 min after stimulation and is followed by a hormone-induced re-acylation process in which excess released arachidonate is re-esterified into cellular lipids. The adenine nucleotides ATP and ADP induce a less selective lipolytic reaction which results in the hydrolysis of arachidonic and linoleic acids. This lipolytic process is less coupled to arachidonic oxygenation as evident from the 1 min delay between arachidonate release and prostaglandin generation. Arachidonate released by the nucleotides orginates from a lipid pool which has a higher turnover and readily incorporates exogenous acid. Generation of oxygenated products from administered exogenous acid is the least coupled process with apparent conversion of only 1-4% to prostaglandin products, amongst which 6-keto-PGF_1α predominates.