A Radioimmunoassay for Rat Plasma ACTH

Rees, Lesley; Cook, David M.; Kendall, John W.; Allen, Catherine F.; Kramer, Rosanne M.; Ratcliffe, John G.; Knight, R A

doi:10.1210/endo-89-1-254

Cited by 479 publications

(159 citation statements)

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“…Hormone determination ACTH, CRH-41, AVP, corticosterone and cyclic AMP were each determined in duplicate by radioimmunoassay using modifications of methods described elsewhere (Rees et al, 1971;Negro-Vilar et al, 1979;Al Dujaili et al, 1981;Hillhouse & Milton, 1989;Loxley et al, 1993a) International plc., Amersham, U.K.). The antibody (raised in rabbit against rat CRH-41 conjugated with P-gamma-globulin, BGG) cross-reacted with rat/human CRH-41 (100%), oxidised rat/human CRH-41 (75%), rat/human CRH21-49 (35%), rat/ human CRHI,20 (0.1%), rat/human CRH6-33 (0.02%), ovine CRH-41 (9%) and sauvagine (0.035%).…”

Section: Static Incubation Of Anterior Pituitary Segmentsmentioning

confidence: 99%

Stimulation of the hypothalamo‐pituitary‐adrenal axis in the rat by the type 4 phosphodiesterase (PDE‐4) inhibitor, denbufylline

Hadley

Kumari

Cover

et al. 1996

British J Pharmacology

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Preliminary studies in our laboratories showed that the synthetic xanthine analogue denbufylline, a selective type 4 phosphodiesterase (PDE‐4) inhibitor, is a potent activator of the hypothalamo‐pituitary‐adrenal (HPA) axis when given orally to adult male rats. This paper describes the results of experiments in which well established in vivo and in vitro models were used to (a) examine further the effects of denbufylline on HPA function and (b) identify the site and mode of action of the drug within the axis. In vivo, administration of denbufylline (0.1–2.5 mg kg−1, i.p.) produced a significant increase in the serum corticosterone concentration; maximal responses were attained at a dose of 1.0 mg kg−1 (P < 0.01 vs. vehicle control, Scheffe's test). However, when denbufylline was administered by intracerebroven‐tricular injection (0.05‐1 μg kg−1) it failed to influence significantly the serum corticosterone concentration (P > 0.05 vs. vehicle control, Scheffe's test). The adrenocortical responses to peripheral injections of denbufylline (1 mg kg−1, i.p.) were reduced in rats in which the secretion of endogenous corticotrophin releasing factors (CRFs) from the hypothalamus was blocked pharmacologically (P < 0.01 vs. controls, Scheffe's test). However, denbufylline (0.1 mg kg−1, i.p.) potentiated the significant (P < 0.01) increases in serum corticosterone concentration provoked in ‘CRF blocked rats’ by hypothalamic extract (5 hypothalamic extracts kg−1, i.v.) although it failed to influence (P > 0.05) the relatively moderate increases in corticosterone secretion evoked by CRH‐41 (2 mg kg−1, i.v.). In vitro, denbufylline (0.01‐1 mM) evoked small but significant (P < 0.05) increases in the release of ACTH from rat anterior pituitary segments; furthermore, at these and lower concentrations (0.01 μm‐1 mM), it potentiated the adrenocorticotrophic responses to sub‐maximal concentrations of hypothalamic extract (P < 0.01) and forskolin (0.1 mM, P < 0.01) but not those to CRH‐41 (10 nM) or 8‐bromo‐cyclic AMP (1–100 μm). In addition, denbufylline (0.1 mM) increased the anterior pituitary cyclic AMP content (P < 0.05) and potentiated the rises in tissue content of the cyclic nucleotide induced by hypothalamic extract (0.1 hypothalamic equivalents ml−1, P < 0.01) and forskolin (0.1 mM, P < 0.01) but not by CRH‐41 (10 nM, P < 0.05). By contrast, denbufylline (1 μm‐1 mM) failed to influence the release of AVP from rat isolated hypothalami and stimulated the secretion of CRH‐41 (P < 0.01) release only at the highest concentration tested (1 mM). The results suggest that the stimulatory actions of denbufylline on the hypothalamo‐pituitary‐adrenocortical axis are exerted predominantly at the level of the anterior pituitary gland and that they may be attributed, at least in part, to inhibition of type 4 phosphodiesterase enzymes.

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Section: Static Incubation Of Anterior Pituitary Segmentsmentioning

confidence: 99%

Stimulation of the hypothalamo‐pituitary‐adrenal axis in the rat by the type 4 phosphodiesterase (PDE‐4) inhibitor, denbufylline

Hadley

Kumari

Cover

et al. 1996

British J Pharmacology

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show abstract

“…Glucocorticoid feedback at the hippocampal and hypothalamic levels is a well-recognised mechanism for inhibiting basal and stress-induced HPA axis activity (for a review see De Kloet et al 1998), but there is also considerable evidence for the existence of non-glucocortocoid mechanisms of inhibition. In adrenalectomised animal models, basal plasma ACTH concentrations are elevated but not maximally, since stressors such as ether (Rees et al 1971), restraint (Chowdrey et al 1991) and haemorrhage (Darlington et al 1990) are capable of further stimulating ACTH release. In addition, a chronic osmotic stimulus inhibits ACTH release through a mechanism which, because it occurs in adrenalectomised rats, cannot be regulated by glucocorticoids ( Jessop et al 1990).…”

Section: Introductionmentioning

confidence: 99%

Review: Central non-glucocorticoid inhibitors of the hypothalamo-pituitary-adrenal axis

Jessop

1999

Journal of Endocrinology

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“…In the present study, the adrenocorticotropic hyperfunction in the hypothalamopituitary system was caused by stress (Vernikos-Danellis, 1963 and1965;Skellaris and Vernikos-Danellis, 1975), metyrapone (Liddle et al, 1959;Oppenheimer et al, 1961;Katsuki et al, 1967) and adrenalectomy (Vernikos-Danellis, 1963and 1965Rees et al, 1971;Yasuda et al, 1976) …”

mentioning

confidence: 50%

Effect of stress, metyrapone and adrenalectomy on compensatory ovarian hypertrophy.

Yaginuma

Kobayashi

1977

Endocrinol Japon

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A Radioimmunoassay for Rat Plasma ACTH

Cited by 479 publications

References 0 publications

Stimulation of the hypothalamo‐pituitary‐adrenal axis in the rat by the type 4 phosphodiesterase (PDE‐4) inhibitor, denbufylline

Stimulation of the hypothalamo‐pituitary‐adrenal axis in the rat by the type 4 phosphodiesterase (PDE‐4) inhibitor, denbufylline

Review: Central non-glucocorticoid inhibitors of the hypothalamo-pituitary-adrenal axis

Effect of stress, metyrapone and adrenalectomy on compensatory ovarian hypertrophy.

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