Role of mitochondrial Ca2+ in antidiuretic hormone action.
The calcium ion concentration measured in rat kidney mitochondria, isolated from vasopressin treated tissue, has a dose response characteristic in which the calcium concentration reached a minimum at low doses of vasopressin (2 mU/ml), at higher doses of hormone the mitochondrial calcium ion concentration increases reaching a value close to that of the controls with vasopressin (100 mU/ml). This efflux and subsequent uptake of mitochondrial calcium has been shown to be a direct effect of the varying cyclic AMP concentrations. Sodium and water permeability effects of vasopressin have been shown in toad bladder to have different dose response characteristics. Maximum sodium transport occurs at a lower dose of vasopressin (2 mU/ml) and is believed to be associated with direct permeability effects of the hormone. Maximum water transport occurs at a higher dose of vasopressin (100 mU/ml) over a concentration range associated with hormone-stimulated adenylate cyclase activity. The water transport response to low doses of vasopressin may be potentiated by aldosterone treatment, an effect that can be related to the inhibition of tissue phosphodiesterase activity and subsequent increased cyclic AMP concentrations. In steroid depleted conditions the cyclic AMP medicate efflux of mitochondrial calcium ions, that occurs at low doses of vasopressin, may prevent the release of membrane bound calcium ions and thus inhibit the water permeability effect of the hormone. Higher levels of cyclic AMP reverse this inhibitory effect and give rise to an increased water flow. It is concluded that cyclic AMP and intracellular concentrations of calcium ion act as inter-related mediators of antidiuretic hormone action.
D000249:Adenosine Monophosphate / Q000494:pharmacology; D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D001834:Body Water / Q000378:metabolism; D002024:Bufo marinus; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010539:Permeability; D012964:Sodium / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology*
D014667:Vasopressins; D000249:Adenosine Monophosphate; D000450:Aldosterone; D012964:Sodium; D000242:Cyclic AMP; D002118:Calcium