EFFECTS OF PROSTAGLANDIN E2 AND DIBUTYRYL CYCLIC AMP ON THE HISTAMINE-INDUCED PRODUCTION OF CORTISOL AND CORTICOSTERONE IN ISOLATED CANINE ADRENAL CELLS

1979 ◽  
Vol 82 (2) ◽  
pp. 275-277 ◽  
Author(s):  
T. HIROSE ◽  
I. MATSUMOTO ◽  
T. AIKAWA

SUMMARY The steroidogenic effect of histamine in isolated adrenocortical cells of the dog was investigated in the presence of prostaglandin E2 (PGE2) and/or dibutyryl cyclic AMP (dbcAMP) in the medium. The effect of histamine, in combination with PGE2, was less than their total individual effects in the production of cortisol, but not of corticosterone. With dbcAMP the effect was just equal to them. However, the combination of histamine, PGE2 and dbcAMP showed an increase twice that of their total individual effects in the production of both steroids. These results indicate that, in the dog, histamine, PGE2 and dbcAMP may act synergistically in the adrenocortical cells.

1977 ◽  
Vol 72 (3) ◽  
pp. 757-763 ◽  
Author(s):  
A T Suyama ◽  
J A Long ◽  
J Ramachandran

The effects of ACTH, its o-nitrophenyl sulfenyl derivative (NPS-ACTH) and dibutyryl cyclic AMP (dbc AMP) on the ultrastructural morphology of adrenocortical cells of adult rats in monolayer culture have been investigated. NPS-ACTH, which has previously been shown to stimulate steroidogenesis but not cAMP synthesis in adrenal cells, induced the same characteristic transformation of mitochondrial architecture as produced by ACTH or high concentrations of dbcAMP. All three agents caused the disappearance of electron-opaque granules present in the mitochondria of unstimulated cells. It was found that these granules could be extracted with EGTA (ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetate). These results are discussed in the light of the known importance of calcium ions in the actions of ACTH.


1983 ◽  
Vol 98 (3) ◽  
pp. 357-363 ◽  
Author(s):  
Nobuyuki Takasu ◽  
Kazunori Takahashi ◽  
Tatsuro Ishigami ◽  
Takashi Yamada ◽  
Seiya Sato

The human thyroid contained prostaglandin (PG) E2, PGF2α and 6-oxo-PGF1α, an end-metabolite of prostacyclin (PGI2), the 6-oxo-PGF1α content being the highest of these prostaglandins. Graves's thyroid contained a significantly higher amount of PGF2α and lower amounts of PGE2 and 6-oxo-PGF1α than the normal thyroid. Thyrotrophin acutely augmented the thyroid contents of PGE2, PGF2α and 6-oxo-PGF1α. The TSH-stimulated increases in PGE2 and 6-oxo-PGF1α were lower but the TSH-stimulated increase in PGF2α was significantly higher in Graves's thyroid than in the normal thyroid. Prostaglandin E2 and PGI2 stimulated human thyroid cyclic AMP synthesis, with the magnitudes of PGE2-and PGI2-stimulated increases in cyclic AMP being equal in normal and Graves's thyroid. Prostaglandin E2α did not stimulate cyclic AMP synthesis significantly. These results provide evidence that prostaglandins play important roles in thyroid physiology and the pathophysiology of Graves's disease.


1981 ◽  
Vol 97 (2) ◽  
pp. 281-288 ◽  
Author(s):  
Ulf Lerner ◽  
Gunnar T. Gustafson

Abstract. The effect of dibutyryl cyclic AMP (dbcAMP) and the phosphodiesterase inhibitors 3-isobutyl methylxanthine (IBMX) and theophylline on bone resorption was studied in an organ culture system for 96– 144 h using half calvaria from 6–7 day old mice. The magnitude of resorption was assessed by measuring the release from the bones of previously incorporated 45Ca. It was observed that dbcAMP, IBMX and theophylline, following a lag period or a period of reduced bone resorption, all progressively increased mineral mobilization. Although the continuous presence of dbcAMP increased mineral mobilization more than a temporary exposure, a limited treatment of 24 h with the nucleotide was sufficient to bring about the delayed stimulatory response. It is concluded that the observations support our earlier proposal that cAMP is not a mediator of the early stages of parathyroid hormone (PTH)- and prostaglandin E2 (PGE2)-stimulated bone resorption. We suggest that the role played by cAMP may be related to the capacity of PTH and PGE2 to develop new osteoclasts, a phenomenon which takes more than 24 h to be observed.


1988 ◽  
Vol 117 (1) ◽  
pp. 109-114 ◽  
Author(s):  
N. Takasu ◽  
T. Yamada ◽  
Y. Shimizu

ABSTRACT Thyrotrophin (TSH) and prostaglandin E2 (PGE2) increased cellular cyclic AMP (cAMP), calmodulin levels and cAMP phosphodiesterase activity in cultured porcine thyroid cells. Dibutyryl cAMP (dbcAMP), a stable analogue of cAMP, increased calmodulin levels and cAMP phosphodiesterase activity. These results indicate that TSH- and PGE2-stimulated increases in calmodulin are mediated by cAMP. This increased concentration of calmodulin in turn stimulates cAMP phosphodiesterase. Double reciprocal plots of cAMP hydrolysis yielded two apparent Michaelis constants (Km); the lower in the 1 μmol/l and the higher in the 10 μmol/l range. Thyrotrophin, PGE2 and dbcAMP increased the values of maximal velocity without changing the Km values. J. Endocr. (1988) 117, 109–114


1980 ◽  
Vol 186 (2) ◽  
pp. 599-603 ◽  
Author(s):  
A F Bristow ◽  
C Gleed ◽  
J L Fauchère ◽  
R Schwyzer ◽  
D Schulster

Comparative studies on the mechanism of action of ACTH1-39 and ACTH5-24 [corticotropin-(1-39)- and corticotropin-(5-24)-peptides] on isolated rat adrenal cells were performed. The relationship between stimulated steroidogenesis and cyclic AMP was very different, suggesting that cyclic AMP does not play the same role in mediating the action of the two agonists. Data from three separate experiments showed that the competitive antagonist ACTH6-24 [corticotropin-(6-24)-peptide] had mean inhibitor constants of 13.4 +/- 3.1 nM against ACTH1-39 and 3.4 +/- 1.0 nM against ACTH5-24, indicating that the steroidogenic actions of these two agonists are mediated by two different receptor types. We conclude that there are two possible mechanisms for corticotropin action, only one of which involves the necessary production of cyclic AMP.


1989 ◽  
Vol 49 ◽  
pp. 70
Author(s):  
Kazutoshi Yanagibashi ◽  
Keiko Hayashida ◽  
Yuji Ohno ◽  
Noboru Nakamichi ◽  
Masahiro Kawamura

1983 ◽  
Vol 104 (1) ◽  
pp. 117-122 ◽  
Author(s):  
Mitsuko Tsuji ◽  
Yukio Kato ◽  
Yoshio Nomura ◽  
Masahiko Kinoshita ◽  
Yuichi Kumahara ◽  
...  

Abstract. Multiplication-stimulating activity (MSA), a somatomedin purified from conditioned medium of Buffalo rat liver cells, had little effect on the intracellular level of cyclic AMP when it markedly enhanced the synthesis of sulphated glycosaminoglycans in rabbit chondrocytes in culture. In addition, MSA did not inhibit prostaglandin E1- or parathyroid hormone-induced accumulation of cyclic AMP in the chondrocytes. On the contrary, MSA slightly decreased stimulation of cyclic AMP accumulation by prostaglandin in human fibroblasts. Dibutyryl cyclic AMP and MSA increased the incorporation of [35S]sulphate and [3H]serine into proteoglycans synthesized by rabbit chondrocytes, and their effects were additive. These findings suggest that somatomedin and dibutyryl cyclic AMP enhance sulphate proteoglycan synthesis through different mechanisms. The lack of inhibitory effect of MSA on cyclic AMP accumulation may be favourable for producing additive effects with cyclic AMP on proteoglycan synthesis and DNA synthesis in chondrocytes.


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