The Effect of Parathyroid Hormone on the Concentration of Adenosine 3',5'-Monophosphate in Skeletal Tissue in Vitro

• Published in: The Journal of biological chemistry 1970-04, Vol.245 (7), p.1520-1526
• Main Authors: Chase, L R, Aurbach, G D
• Format: Article
• Language: English
• Subjects: Adenine Nucleotides - metabolism; Adenylyl Cyclases - metabolism; Adrenergic beta-Antagonists - pharmacology; Animals; Bone and Bones - drug effects; Bone and Bones - embryology; Bone and Bones - enzymology; Bone and Bones - metabolism; Calcitonin - pharmacology; Calcium - pharmacology; Cattle; Cholestanes - pharmacology; Cyclic AMP - metabolism; Depression, Chemical; Enzyme Activation; Epinephrine - antagonists & inhibitors; Epinephrine - pharmacology; Female; Fluorides - pharmacology; Guanine Nucleotides - pharmacology; Hormones - pharmacology; In Vitro Techniques; Magnesium - pharmacology; Parathyroid Hormone - antagonists & inhibitors; Parathyroid Hormone - pharmacology; Peptides - pharmacology; Phentolamine - pharmacology; Phosphoric Monoester Hydrolases - metabolism; Potassium - pharmacology; Pregnancy; Propranolol - pharmacology; Prostaglandins - pharmacology; Rats; Skull - metabolism; Sterols - pharmacology; Stimulation, Chemical
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(19)77126-9

Adenosine 3',5'-monophosphate (3',5'-AMP) was assayed in calvaria isolated from fetal rats at term. A marked increase in 3',5'-AMP was detected in vitro within 1 min after adding purified parathyroid hormone to calvaria incubated in Krebs-Ringer-bicarbonate or Krebs-Ringer-Tris buffer. A maximal effect was detected after 5 min of incubation with added parathyroid hormone. The lowest concentration of parathyroid hormone causing a significant effect was 0.05 µg per ml or 5 x 10 -9 m . The response was a direct function of the log concentration of parathyroid hormone from 0.1 to 1.0 µg per ml, became maximal at 10 µg per ml, did not require potassium, magnesium, or calcium in the incubation medium, and was not inhibited by a high (5 m m ) concentration of calcium. Epinephrine and prostaglandins E 1 and E 2 also caused a significant increase in skeletal 3',5'-AMP. The effect of epinephrine was abolished by propranolol, but this β-adrenergic blocking agent did not affect the response to the prostaglandins or to parathyroid hormone; phentolamine did not affect the response to any of these substances. Calcitonin caused a slight increase in skeletal 3',5'-AMP, but the maximal effect was small and the response was not related to the concentration of polypeptide. Only the effect of parathyroid hormone was clearly relatable to direct hormonal activation of adenyl cyclase in the tissue. Neither thyrotropin, corticotropin, glucagon, insulin, luteinizing hormone, growth hormone, adenosine 5'-monophosphate, guanosine 3',5'-monophosphate, 25-hydroxycholecalciferol, nor sodium fluoride affected the concentration of 3',5'-AMP in this test system. These findings provide further evidence that the physiological actions of parathyroid hormone are mediated by 3',5'-AMP.