Cell-specific coupling of PGE2 to different transduction pathways in arginine vasopressin- and glucagon-sensitive segments of the rat renal tubule

1 The aim of the present study was to investigate the transduction pathways elicited by prostaglandin E-2 (PGE(2)) to inhibit hormone-stimulated adenosine 3 ':5 '-cyclic monophosphate (cyclic AMP) accumulation in the outer medullary collecting duct (OMCD) and medullary thick ascending limb (MTAL) microdissected from the rat nephron. 2 In the OMCD, 0.3 mu M PGE(2) and low concentrations of Ca2+ ionophores (10 nM ionomycin or 50 nM A23187) inhibited by about 50% a same pool of arginine vasopressin (AVP)-stimulated cyclic AMP content through a same process insensitive to Bordetella pertussis toxin (PTX). 3 Sulprostone, an agonist of the EP1/EP3 subtypes of the PGE(2) receptor, decreased AVP-dependent cyclic AMP accumulation in OMCD and MTAL samples. The concentration eliciting half-maximal inhibition was of about 50 nM in OMCD and 0.1 nM in MTAL. 4 In MTAL, 1 nM sulprostone and PGE(2) inhibited by about 90% a same pool of AVP-dependent cyclic AMP content through a PTX-sensitive, Ca2+-independent pathway. 5 In the OMCD, PGE(2) decreased by about 50% glucagon-dependent cyclic AMP synthesis by a process sensitive to PTX and Ca2+-independent. Sulprostone 1 nM induced the same level of inhibition. 6 These results demonstrate that PGE(2) decrease hormone-dependent cyclic AMP accumulation through a G alpha i-mediated inhibition of adenylyl cyclase activity in MTAL cells and glucagon-sensitive cells of the OMCD or through a PTX-insensitive increase of intracellular Ca2+ concentration in AVP-sensitive cells of the OMCD.