Interaction between arginine vasopressin- and raised extracellular potassium-stimulated pathways in...

The intracellular regulation of adrenocorticotropin (ACTH) secretion from pituitary corticotroph cells was investigated by simultaneously exposing cultured ovine corticotrophs to arginine vasopressin (AVP) and raised extracellular K+ concentration ([K+]e). Both of these secretagogues activate L-type voltage-sensitive calcium channels (L-VSCC) as part of their respective ACTH secretory responses. When given together at high concentrations, AVP and raised [K+]e caused ACTH responses that were smaller in magnitude than the sum of the individual responses. However, at low agonist concentrations the simultaneous responses were greater in magnitude (i.e., synergistic). Further investigation suggested that activation of protein kinase C (PKC), which is part of the AVP-induced intracellular signalling pathway, is necessary and sufficient for the generation of the synergistic response, although it is not obligatory for AVP-induced ACTH release.