Impaired agonist-induced calcium signaling in hepatocytes from chronic renal failure rats.
Some hormones exert their action by inducing a rise in cytosolic calcium [Ca2+]i (calcium signal), and therefore, a blunting in hormone-induced calcium signal would engender resistance to the action of the hormone. Chronic renal failure (CRF) is associated with resistance to the action of a variety of hormones, a rise in [Ca2+]i and decrease in the amount of mRNA of one hormone receptor, the PTH-PTHrP receptor. We examined the calcium-signal induced by PTH, angiotensin II, vasopressin and glucagon in hepatocytes from CRF animals, evaluated the effect of the basal level [Ca2+]i on the calcium signal and explored the effect of [Ca2+]i on the mRNA of the receptors of these agonists. Hepatocytes from CRF rats have elevated basal levels of [Ca2+]i and display significantly reduced calcium signals induced by all these hormones, while the calcium signals were normal in PTX-CRF animals and those treated with verapamil both of which have normal levels of [Ca2+]i despite CRF. The calcium signals induced by dibutyryl cyclic AMP and G protein activator (GTP gamma S) were normal in hepatocytes from CRF animals despite the high levels of [Ca2+]i. Northern blotting experiments revealed that the levels of the mRNA of the receptors of PTH-PTHrP, angiotensin II and vasopressin were significantly reduced in hepatocytes from CRF animals but PTX-CRF rats and those treated with verapamil had either significantly greater or even normal amounts of the mRNA of these receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Massry
S G
SG
Department of Medicine, University of Southern California, School of Medicine, Los Angeles, USA.
Klin
M
M
Ni
Z
Z
Tian
J
J
Kedes
L
L
Smogorzewski
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology; D016105:Parathyroidectomy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044168:Receptor, Parathyroid Hormone, Type 1; D011956:Receptors, Cell Surface / Q000235:genetics; D018016:Receptors, Parathyroid Hormone / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D006728:Hormones; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D044168:Receptor, Parathyroid Hormone, Type 1; D011956:Receptors, Cell Surface; D018016:Receptors, Parathyroid Hormone; D014700:Verapamil; D002118:Calcium