PGE₂ and PGI₂ stimulate renin secretion and cAMP accumulation in juxtaglomerular granular (JG) cells. We addressed, at the single cell level, the receptor subtypes and intracellular transduction mechanisms involved. Patch clamp was used to determine cell capacitance (C_m), current and membrane voltage in response to PGE2, EP2 and EP4 receptor agonists and an IP receptor agonist. PGE₂ (0.1 µmol/L) increased C_m significantly and the increase was abolished by intracellular application of the protein kinase A antagonist, Rp-8-CPT-cAMPS. EP2-selective ligands (butaprost 1 µmol/L, AE1-259-01 1 nmol/L), EP4-selective agonist (AE1-329 1 nmol/L) and IP agonist (iloprost 1 µmol/L) significantly increased C_m mediated by PKA. EP4 antagonist (AE3-208 10 nmol/L) blocked the effect of EP4 agonist, but did not alter the response to PGE₂. Application of both EP4 antagonist and EP2-antagonist, AH6809, abolished the effects of PGE₂ on C_m and current. EP2 and EP4 ligands stimulated cAMP formation in JG-cells. PGE₂ rapidly stimulated renin secretion from superfused JG-cells and diminished the membrane-adjacent granule pool as determined by confocal microscopy. The membrane potential hyperpolarized significantly after PGE₂, butaprost, AE1-329 and AE1- 259 and outward current was augmented in a PKA-dependent fashion. PGE₂-stimulated outward current, but not C_m change, was abolished by the BK_Ca channel inhibitor iberiotoxin (300 nmol/L). EP2 and EP4 mRNA was detected in sampled JG-cells and the preglomerular and glomerular vasculature was immunopositive for EP4. Thus, IP, EP2 and EP4 receptors are associated with JG-cells and their activation leads to rapid PKA-mediated exocytotic fusion and release of renin granules.