title: Activation of separate calcium and A-kinase-dependent pathways by ACTH.
abstract: Although cAMP has long been regarded as the primary intracellular messenger for ACTH-stimulated cortisol secretion, a requirement for Ca2+ is well established. However, a specific mechanism which couples ACTH receptor activation to increased intracellular calcium concentration in the adrenal cortical cell has not been elucidated. Here, we present evidence for a specific model in which ACTH at picomolar concentrations induces cAMP which acts through kinase-dependent and independent pathways to stimulate cortisol secretion. Along one of these pathways, cAMP acts directly to depolarize cells by inhibition of a specific non-inactivating K+ channel (I(AC)). This model provides a specific mechanism whereby cAMP-mediated inhibition of I(AC) is tightly coupled to depolarization-dependent Ca2+ entry and cortisol secretion. Ca2+ and cAMP are dual second messengers in the ACTH signalling pathway that are linked through I(AC) K+ channels.
authors.affiliation: Department of Pharmacology and The Neuroscience Program, The Ohio State University College of Medicine, Columbus, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Enyeart
authors.forename: J A
authors.initials: JA
authors.lastname: Enyeart
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002417:Cattle; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D026902:Potassium Channel Blockers; D015290:Second Messenger Systems / Q000502:physiology
chemical_list: D026902:Potassium Channel Blockers; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium