Prostaglandin E₂ synthesis in the inner medullary collecting duct of the rat: Implications for vasopressin‐dependent cyclic AMP formation

The effects of osmolality on prostaglandin E₂ (PGE₂) biosynthetic capacity and the interaction between endogenous PGE₂ synthesis and vasopressin (AVP)‐dependent cyclic AMP generation were examined in papillary collecting ducts (PCD) microdissected from collagenase‐digested rat kidneys. Increasing medium osmolality with NaCl:urea (1:2 molar ratio) progressively increased PGE₂ synthesis in PCD up to 1,500 mOsm. Addition of NaCl:urea or NaCI alone were equally effective in stimulating PGE₂ biosynthetic capacity in PCD. In contrast, addition of urea alone had a much smaller stimulatory effect on PGE₂ synthesis. Inhibition of endogenous PGE₂ synthesis with naproxen (10⁻⁵M) suppressed AVP‐dependent cAMP formation in PCD when incubated in 300 mOsm medium but had no effect when incubated in 1,500 mOsm medium. Addition of 2.5×10⁻⁵ M PGE₂ also suppressed AVP‐dependent cAMP formation in PCD only when incubated in 300 mOsm medium. The present study suggests that the PCD is a site of active PGE₂ synthesis that is modulated by osmolality. Our results do not support the concept that endogenous PGE₂ antagonizes vasopressin action via inhibition of AVP‐dependent cAMP formation.