Biomedical subjects

J W Funder

Publications and source records attributed to J W Funder.

346 records · Page 20Linked to original sources

PubMedDate not supplied

Stress, dopaminergic blockade and median eminence-neurointermediate lobe catecholamine depletion: effects on hypothalamic, pituitary and plasma immunoreactive beta-endorphin.

We have compared immunoreactive beta-endorphin (ir-beta EP) levels in plasma, hypothalamus, anterior pituitary and neurointermediate lobe of adult female Sprague-Dawley rats, in studies in which levels of catecholamines were manipulated. Whole-brain catecholamines were manipulated by intraperitoneal haloperidol and/or bromocriptine; median eminence and neurointermediate lobe catecholamines were manipulated specifically and differentially by intravenous 6-hydroxydopamine (6-OHDA), with and without pretreatment with intraperitoneal desipramine; changes in amine neurons were assessed by fluorescence histochemistry. Haloperidol and 6-OHDA administration produced a selective reduction of neurointermediate lobe ir-beta EP, to levels equivalent to those seen with prolonged stress; the haloperidol effect was blocked by bromocriptine and the 6-OHDA effect by desipramine. Specific depletion of catecholamine nerve terminals in the median eminence and the neurointermediate lobe was associated with elevated plasma ir-beta EP, with no changes in pituitary or hypothalamic levels. These studies confirm and extend previous reports documenting that ir-beta EP levels in different tissues are modulated by different neural stimuli.

Animals↗

PubMedDate not supplied

Further studies on neomycin and experimental hypertension.

Acute glucocorticoid (corticosterone) hypertension in the rate is significantly attenuated by neomycin administration (Honour 1981), as is ACTH-induced hypertension is the same species (Honour & Kent 1981) presumably by altering gut bacterial steroid metabolism. The effect on blood pressure of oral neomycin administration was therefore examined in hypertension resulting from administration of a variety of glucocorticoid hormones. Neomycin significantly attenuated the elevation of blood pressure following ACTH or corticosterone, as previously shown, or prednisolone 1 mg/day; it did not affect blood pressure in rats given dexamethasone 0.2 mg/day, or cortisol 4 mg twice daily. Since the differential effect of neomycin on hypertension parallels neither pressor nor glucocorticoid activity of the administered steroids we propose that it reflects different patterns of enterohepatic handling and metabolism.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

High affinity aldosterone binding sites (type I receptors) in rat heart.

1. The use of the receptor stabilizing agent sodium molybdate, and of RU26988 to exclude [3H]-aldosterone binding from Type II glucocorticoid receptors, has enabled the characterization of high affinity Type I aldosterone binding sites in rat atrial and ventricular cytosols. 2. In adult male and female rats the affinity of binding (Kd 4 degrees C) is approximately 1-2 nmol/l for both atria and ventricles; specificity of binding is similar to that for Type I sites in classical aldosterone target tissues (aldosterone = corticosterone much greater than dexamethasone). 3. Levels of atrial Type I sites are higher than the corresponding levels in ventricle in both males and females, whereas for Type II (classical glucocorticoid) receptors the reverse is the case; levels of both Type I and Type II sites fall over the age range examined (40 days-6 months). 4. The physiological function(s) of cardiac Type I sites, and their in vivo mineralocorticoid or glucocorticoid selectivity, remain to be explored.

Adrenalectomy↗

PubMedDate not supplied

Aldosterone, salt and cardiac fibrosis.

The classical effects of aldosterone are mediated via epithelial mineralocorticoid receptors (MR), protected against cortisol/corticosterone occupancy and activation by the enzyme 11 beta hydroxysteroid dehydrogenase. The pathophysiological effects of aldosterone on non-epithelial tissues, in contrast, are mediated via unprotected MR in which occupancy by cortisol/corticosterone antagonises the effect of aldosterone. Aldosterone raises blood pressure by occupying MR in the circumventricular region of the brain, an effect antagonised by concomitant intracerebroventricular (ICV) infusion of similar doses of corticosterone. Peripheral infusion of aldosterone to salt loaded rats causes hypertension, cardiac hypertrophy and cardiac fibrosis; concomitant ICV infusion of the MR antagonist RU28318 abolishes the aldosterone-induced hypertension, but does not affect cardiac hypertrophy or fibrosis. These peripheral effects of aldosterone are presumably via cardiac MR; high glucose/PKC modulated, aldosterone-specific effects on protein synthesis have recently been demonstrated as direct MR-mediated actions on cultured neonatal rat cardiomyocytes. The pathophysiologic effects of aldosterone via nonepithelial MR have a time course of days/weeks rather than hours, reflect occupancy of only a small percentage of such receptors, and require salt loading. How the effects of salt loading are transduced in such circumstances remains to be explored.

11-beta-Hydroxysteroid Dehydrogenases↗