Synthetic parathyroid hormone fragments shortened at the amino terminus stimulate glucose-6-phosphate dehydrogenase activity in the distal renal tubule.
The cytochemical bioassay, using glucose-6-phosphate dehydrogenase (G6PD) activity in the distal convoluted tubule of a guniea pig as an index, is specific and the most sensitive method of evaluating the biological activity of parathyroid hormone (PTH). Using this method, biological activities of the amino- or carboxyl-terminal PTH fragments and analogues, human (h) PTH-(3-34), [Tyr34]hPTH-(7-34)amide(NH2), [Tyr34]hPTH-(13-34)NH2, hPTH-(39-84), hPTH-(51-84), hPTH-(69-84), were tested over a concentration range of 10(-16) to 10(-13) M. In addition, the combined effect of these hormones with human or bovine PTH-(1-84) and the effect of dibutyryl (Bu)2) cAMP were also evaluated. In the 14-min time-course study, amino-terminal PTH fragments and analogues induced cyclic changes of G6PD activity with shorter cycle lengths in higher concentrations and with constant peak heights regardless of the concentrations. Human and bovine PTH-(1-84) showed the same activity on G6PD activation at 6 min. hPTH-(3-34), [Tyr34]hPTH-(7-34)NH2, and [Tyr34]hPTH-(13-34)NH2 were equipotent with PTH-(1-84) on a molar basis, and none of these analogues inhibited PTH-(1-84) even with doses up to 240 times that of PTH-(1-84). Carboxyl-terminal PTH showed no effect. (Bu)2cAMP mimicked the effect of PTH-(1-84) on G6PD activation in time course and dose response. We conclude that the amino terminus is not essential for the biological activity of PTH in the cytochemical bioassay.
Sakaguchi
K
K
Department of Medicine, Kobe University School of Medicine, Japan.
Fukase
M
M
Kobayashi
I
I
Kimura
T
T
Sakakibara
S
S
Katsuragi
S
S
Morita
K
K
Noda
T
T
Fujita
T
T
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D006168:Guinea Pigs; D006651:Histocytochemistry; D007684:Kidney Tubules / Q000201:enzymology*; D007686:Kidney Tubules, Distal / Q000201:enzymology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D003994:Bucladesine; D000242:Cyclic AMP; D005954:Glucosephosphate Dehydrogenase