Two Possibly Distinct Prostaglandin E₁ Receptors in N1E‐115 Clone: One Mediating Inositol Trisphosphate Formation, Cyclic GMP Formation, and Intracellular Calcium Mobilization and the Other Mediating Cyclic AMP Formation

Prostaglandin E₁ (PGE₁)‐mediated transmembrane signal control systems were investigated in intact murine neuroblastoma cells (clone N1E‐115). PGE₁ increased intra‐cellular levels of total inositol phosphates (IP), cyclic GMP, cyclic AMP, and calcium ([Ca²⁺]i). PGE₁ transiently increased inositol 1,4,5‐trisphosphate formation, peaking at 20 s. There was more than a 10‐fold difference between the ED₅₀ for PGE₁ at cyclic AMP formation (70 nM) and its ED₅₀ values at IP accumulation (1 μM), cyclic GMP formation (2 μM), and[Ca²⁺]_i increase (5 μM). PGE₁‐mediated IP accumulation, cyclic GMP formation, and [Ca²⁺]_i increase depended on both the concentration of PGE₁ and extracellular calcium ions. PGE₁ had more potent intrinsic activity in cyclic AMP formation, IP accumulation, and cyclic GMP formation than did PGE₂, PGF_2α, or PGD₂. A protein kinase C activator, 4β‐phorbol 12β‐myristate 13α‐acetate, had opposite effects on PGE₁‐mediated IP release and cyclic GMP formation (inhibitory) and cyclic AMP formation (stimulatory). These data suggest that there may be subtypes of the PGE₁ receptor in this clone: a high‐affinity receptor mediating cyclic AMP formation, and a low‐affinity receptor mediating IP accumulation, cyclic GMP formation, and intracellular calcium mobilization.