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Rat kidney cells in primary culture: hormone-mediated desensitization of the adenosine 3',5'-monophosphate response to parathyroid hormone and calcitonin. 1982

W I Chao, and L R Forte

To investigate the direct actions and the possible cellular mechanisms of parathyroid hormone (PTH) and salmon calcitonin (sCT) action in inducing the desensitization of renal cAMP responses to these hormones, we studied kidney cells in primary culture. Renal cells isolated from neonatal rats were cultured in F-12 medium plus 100 microliters/ml calf serum. The cultured kidney cells reached confluent monolayer in 24 h and remained responsive to hormones, including PTH, sCT, vasopressin, and prostaglandin E1. Pretreatment of the cultured cells with PTH (2.5 X 10(-7) M) or sCT (3 X 10(-7) M) resulted in homologous desensitization in the cAMP responses to these hormones. Both PTH- and sCT-mediated desensitization were time and dose dependent. The EC50 for PTH-mediated desensitization was approximately 3.2 X 10(-9) M, and that for sCT was 2.0 X 10(-10) M. Cells that were desensitized to PTH or sCT showed normal responsiveness to cholera toxin, indicating that the catalytic and coupling units of the adenylate cyclase were not modified, suggesting that the locus for desensitization was at the receptor sites. We also found that the renal cell adenylate cyclase, after stimulation by PTH, was markedly different from that observed with sCT. The cAMP response to PTH was short-lived and readily reversible after removal of the hormone from the medium. Exposure to sCT resulted in stable activation of the adenylate cyclase system which was noted for several hours after the removal of sCT, sCT may form a stable complex with the receptors, thus activating the catalytic unit of the adenylate cyclase for a substantial period of time after removal of the hormone. This mechanism may account for the unique pharmacological efficacy of sCT.

UI MeSH Term Description Entries
D007545 Isoproterenol Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. Isoprenaline,Isopropylarterenol,4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol,Euspiran,Isadrin,Isadrine,Isopropyl Noradrenaline,Isopropylnoradrenaline,Isopropylnorepinephrine,Isoproterenol Hydrochloride,Isoproterenol Sulfate,Isuprel,Izadrin,Norisodrine,Novodrin,Hydrochloride, Isoproterenol,Noradrenaline, Isopropyl,Sulfate, Isoproterenol
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D010281 Parathyroid Hormone A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates. Natpara,PTH (1-84),PTH(1-34),Parathormone,Parathyrin,Parathyroid Hormone (1-34),Parathyroid Hormone (1-84),Parathyroid Hormone Peptide (1-34),Hormone, Parathyroid
D011458 Prostaglandins E (11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities. PGE
D002116 Calcitonin A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. Thyrocalcitonin,Calcitonin(1-32),Calcitrin,Ciba 47175-BA,Eel Calcitonin,Calcitonin, Eel,Ciba 47175 BA,Ciba 47175BA
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000262 Adenylyl Cyclases Enzymes of the lyase class that catalyze the formation of CYCLIC AMP and pyrophosphate from ATP. Adenyl Cyclase,Adenylate Cyclase,3',5'-cyclic AMP Synthetase,Adenylyl Cyclase,3',5' cyclic AMP Synthetase,AMP Synthetase, 3',5'-cyclic,Cyclase, Adenyl,Cyclase, Adenylate,Cyclase, Adenylyl,Cyclases, Adenylyl,Synthetase, 3',5'-cyclic AMP
D000527 Alprostadil A potent vasodilator agent that increases peripheral blood flow. PGE1,Prostaglandin E1,Caverject,Edex,Lipo-PGE1,Minprog,Muse,PGE1alpha,Prostaglandin E1alpha,Prostavasin,Prostin VR,Prostine VR,Sugiran,Vasaprostan,Viridal,Lipo PGE1
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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