Levels of Corticotrophin Analogues in the Blood After Infusion Into Rats

McMartin, Colin; Peters, J A

doi:10.1677/joe.0.0670041

Cited by 16 publications

(8 citation statements)

References 10 publications

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“…The possibility that potentiating factors prevent ACTH proteolysis is proposed. However, it should be noted that a similar potentiating effect has been demonstrated against modified ACTH-(1-19), whose analogous pep tide, (D-Ser1, Lys17, Lys18) ACTH-(1-18) octadecapeptide amide, is shown to be less susceptible to proteolytic degradation than ACTH-(l-24) [17], The results suggest the existence of mechanisms other than the inhibition of ACTH proteolysis.…”

Section: Discussionmentioning

confidence: 52%

Presence of ACTH-Potentiating Factors in Rat Anterior Pituitary Glands

et al. 1981

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High molecular weight ACTH fractions, obtained through gel filtration of boiled rat anterior pituitary extract, induced a marked increase in corticosterone production from isolated rat adrenal cells in the presence of low concentrations of ACTH-(1-24). This indicates the presence of heat-stable factors augmenting the steroidogenic action of ACTH in the rat anterior pituitary. We also noted that these factors potentiated the activity not only of ACTH-(1-24) but also of ACTH-(1–18). The ACTH-potentiating factors in rat anterior pituitary extract are possibly present in heterogeneous forms according to their molecular weights (8,000, 10,000 and 15,000), their mobility in ion-exchange chromatography and their content in RIA-ACTH activity. Of these three forms, the former comigrated with biological ACTH activity. The remaining two forms were free of it. Since the effect of potentiating factors on modified ACTH-(1–19), shown to be less susceptible to proteolytic degradation than ACTH-(l-24), was similar to the effect on ACTH-(1-24), it is suggested that potentiation was not due to an inhibition of ACTH proteolysis.

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Section: Discussionmentioning

confidence: 52%

Presence of ACTH-Potentiating Factors in Rat Anterior Pituitary Glands

et al. 1981

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“…1975) is con¬ sistent with the more rapid breakdown of Synacthen than of ACTH in in¬ cubated foetal blood (Jones, unpublished observations). For comparison, in the rat in vivo human ACTH130 has a much greater metabolic stability than ACTH!-24 (Synacthen; McMartin 8c Peters 1975;McMartin et al 1977). In the foetus the estimation of metabolic clearance rate is particularly dependent on the position of the infusion and sampling catheters.…”

Section: Discussionmentioning

confidence: 99%

Adrenocorticotrophin and Corticosteroid Changes During Dexamethasone Infusion to Intact and Synacthen Infusion to Hypophysectomized Foetuses

Jones

Kendall

Ritchie

et al. 1978

Acta Endocrinologica

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Synacthen has been infused at 10 \g=m\g/h into 4 hypophysectomized foetal sheep. This caused a rise in adrenocorticotrophin to a mean value of 512 pg/ml which remained fairly constant and did not show the large fluctuations seen on infusion into intact foetuses. The Synacthen half-life in the circulation had a mean value of 0.27 min. Hypophysectomy did not necessarily delay the foetal corticosteroid response to Synacthen infusion. The corticosteroid concentration achieved had a mean value of about 50 ng/ml which is substantially below that for intact foetuses and in one case it was maintained at only 20 ng/ml. Despite this delivery occurred within 5 days. Dexamethasone infusion reduced the plasma adrenocorticotrophin concentration by about 70 % and the plasma cortisol concentration by about 60 %.During the induction of premature parturition in sheep by the infusion of Synacthen into the foetus plasma adrenocorticotrophin (ACTH) concentra¬ tions first showed a small increase then this was followed by large fluctuations (Johnson et al. 1975). These results suggested that during Synacthen infusion ® Present address:

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“…This indicated relatively little breakdown of the octadecapeptide by endopeptidases. Consistent with this observation was the survival and relative build-up at 1 h within lysosomes of activity from tritiated octadecapeptide confirming the apparent importance of the kidney in the break¬ down of this peptide (McMartin & Peters, 1975). Interpretation of the quantitative autoradiographic results for the three Synacthen tetracosapeptides tritiated in different positions is not straightforward.…”

Section: Discussionmentioning

confidence: 82%

“…Working with two ACTH analogues, Synacthen (corticotrophin-(l-24)-tetracosapeptide) and C 41795-Ba ([D-Ser1,Lys17,Lys18]-corticotrophin-(l-18)-octadecapeptide amide) and human ACTH, McMartin & Peters (1975) showed that renal ligature of rats significantly decreased the rate of decline of C 41795-Ba and human ACTH following intravenous infusion, but not of the 1-24 peptide. Thus, it would appear that there is a different route for most of the inactivation of the latter analogue.…”

Section: Introductionmentioning

confidence: 99%

Renal Uptake and Metabolism of Adrenocorticotrophin Analogues in the Rat: An Autoradiographic Study

Baker¹,

Bennett²,

Christian³

et al. 1977

Journal of Endocrinology

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Renal resorption of tritiated adrenocorticotrophin analogues was studied in the rat using light microscopic and quantitative electron microscopic autoradiography. The synthetic corticotrophins used were Synacthen (corticotrophin-(1-24)-tetracosapeptide) and C41795-Ba ([D-Ser1,Lys17,Lys18]-corticotrophin-(1-18)-octadecapeptide amide), the tetracosapeptide being tritiated in either the tyrosine residue of position 2 or 23 or the phenylalanine of position 7 and the octadecapeptide in the tyrosine of position 2. Inspection of autoradiographs showed that peptides injected intravenously were resorbed into proximal tubules by endocytosis to produce vesicles whose radiolabel later appeared in lysosomes, a route previously elucidated for other peptides and proteins. The use of two techniques for analysis of electron microscopic autoradiographs, however, suggested that apical tubules also acquire label and are in some way involved in the transfer of resorbed labelled material from endocytotic vesicles to lysosomes. In addition, the autoradiographic analyses revealed that the duration of lysosomal labelling depends upon the position of tritium in the chain. Thus, when the CO2H-terminus of Synacthen was labelled, silver grains were more transiently associated with lysosomes than was the case when the NH2-terminal or core regions were tritiated, indicating a greater resistance of these portions of the peptide to attack by intracellular peptidase. The label from the chemically protected C 41795-Ba was also less readily expelled from the lysosomes of the proximal tubules.

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Levels of Corticotrophin Analogues in the Blood After Infusion Into Rats

Cited by 16 publications

References 10 publications

Presence of ACTH-Potentiating Factors in Rat Anterior Pituitary Glands

Presence of ACTH-Potentiating Factors in Rat Anterior Pituitary Glands

Adrenocorticotrophin and Corticosteroid Changes During Dexamethasone Infusion to Intact and Synacthen Infusion to Hypophysectomized Foetuses

Renal Uptake and Metabolism of Adrenocorticotrophin Analogues in the Rat: An Autoradiographic Study

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