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The effect of environmental tonicity on the interaction between arginine vasopressin (AVP) and prostaglandin (PG) E in the production of adenosine-3’,5’-cyclic monophosphate (cAMP) was studied in cultured rat renal papillary collecting tubule cells. Both AVP and PGE2 stimulated intracellular cAMP accumulation in a dose-dependent manner in an isotonic medium of 300 mOsm/kg H20 in the presence of a phosphodiesterase inhibitor. Environmental tonicity modulated the effect of AVP, PGE, or of both, on cellular cAMP production. The hypertonic medium with 1,800 mOsm/kg H20 enhanced the effect of 1><10_9 M AVP on the cellular cAMP production 1.6-fold, but markedly reduced the effect of 2 >< 10's MPGE, or PGE2 to one-sixth or one-third ofthat in the isotonic medium. The inhibitory effect ofPGE, and PGE,»; on the action ofAVP was not shown in the isotonic medium, but was seen in the hypertonic medium of 1,800 mOsm/kg H20. Synthesis of [3H]PGE2 was enhanced by hypertonicity, but not by AVP, when [3H]arachidonic acid was incorporated in the medium. The results indicate that an environmental tonicity is an important factor in modulating the effect ofPGE, or PGE2 on AVP-mediated cAMP production in renal papillary collecting tubule cells. Since the pioneering study by Orloff and Handler with the toad urinary bladder (28), interaction between arginine vasopressin (AVP) and prostaglandins (PGs) in water permeability has been investigated extensively (1, 10, 18, 24, 25, 27, 35). The action ofAVP on the renal collecting tubule to increase water permeability is mediated by adenosine-3’,5’-cyclic monophosphate (cAMP) (7, 16). The effects ofPGs, however, are still in controversy. PGE, a major product ofPGs Abbreviations.‘ AVP, arginine vasopressin; PG, prostaglandin; -cAMP, adenosine-3',5’-cyclic monophosphate; KRB, Krebs-Ringer buffered saline; Gpp(NH)p, 5"-guanylylimidodiphosphate; IMX, 3-isobutyl-lmethylxanthine in the kidney (32), has been reported to directly stimulate adenylate cyclase activity (10, 12, 14, 18, 25), to inhibit AVP-induced cAMP production in the collecting tubule (11, 24, 32), or to have little effect on the AVP action (8, 18, 34, 35). Similar conflicting results were also shown in amphibian epithelium (27, 28). Discrepancies among the investigators may depend upon factors such as differenoes in tissue preparations, nephron heterogeneity (26), environmental tonicity (21) and others. The effect of environmental tonicity on the interaction between PGE and AVP in cAMP metabolism has not yet been fully elucidated. Jackson er al. (18) and Torikai er al. (35) suggested that some cofactors required to generate cAMP may be lost in preparations of broken cells. Therefore, events in intact cells 2 3

biomedical research

&lt;b&gt;EFFECTS OF OSMOLALITY ON THE INTERACTION BETWEEN VASOPRESSIN AND PROSTAGLANDINS IN RAT RENAL PAPILLARY COLLECTING TUBULE CELLS IN &lt;/b&gt;&lt;b&gt;CULTURE &lt;/b&gt;