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Biomedical subjects

J R Lymangrover

Publications and source records attributed to J R Lymangrover.

At least 19 recordsLinked to original sources
PubMed1988

Rat adrenal zona fasciculata cell electrophysiological responses to ACTH and gamma-MSH vary with age.

A comparison was made of the resting membrane potential (MP) as well as the MP responses to K+, ACTH and gamma-MSH of superfused adrenocortical, zona fasciculata cells from young (Y) and old (O) male rats. The resting MP of these cells did not vary with age. However, the MP responses to altered extracellular [K+] varied significantly with age. A prolonged biphasic depolarization was observed following ACTH administration; these responses were significantly reduced in O cells. In contrast, stimulation with gamma-MSH did not consistently elicit depolarization in the Y but caused a consistent and prominent depolarization in O cells. These findings suggest that aging is associated with changes in primary membrane events which could explain the reduced ACTH-stimulated steroidogenesis associated with age. Elevated cellular responses to gamma-MSH may contribute to a maintenance of, or increase in, circulating corticosterone levels in aged rats.

Adrenal Cortex↗
PubMed1987

Direct power-frequency electric field effects on mammalian endocrine tissue.

A number of studies have investigated the in vivo biological effects of power-frequency electric fields (EF). Direct effects of EF on mammalian tissues, however, have rarely been reported. We now report that a 60-Hz EF can directly enhance the steroidogenic response of superfused rat adrenocortical tissue. The EF did not influence basal steroidogenic activity, however, the corticosterone response to 10 mU of ACTH was almost doubled by an unperturbed 1000 kV/m EF during the initial 2 hr of exposure and was enhanced fourfold by 5.5 to 7 hr of exposure with a 10 kV/m EF. Other EF intensities (e.g., 5 and 100 kV/m) were without effect at these times. Turning the 1000 kV/m EF on and off at 30-min intervals did not influence the initial enhanced steroidogenic response but did cause an additional two- to threefold elevation in the response following 5.5-7 hr of exposure. It is not clear what EF exposure parameters or mechanisms were primarily responsible for these bioeffects, but it appears that direct exposure of mammalian endocrine tissue to a 60-Hz EF is capable of significantly influencing important cellular processes.

Adrenal Cortex↗
PubMed1986

Chronic 60-Hz electric field exposure-induced subtle bioeffects on hematology.

The effects of 120 days of high-intensity (80-kV/m) 60-Hz electric field exposure on hematologic constituents were investigated using a three-generation design including 135 field-exposed and 135 sham-exposed male Sprague-Dawley rats. Statistical tests performed included the multivariate analysis of variance, the univariate analysis of variance, and tests of simple effects. Total white cell count, lymphocyte count, and eosinophil count were significantly lower in field-exposed subjects; however, none of the red cell parameters differed significantly. The observed hematologic variations related to the exposure of a high-intensity electric field are consistent with those observed in animals responding to a mild stressor.

Analysis of Variance↗
PubMed1985

Pressor and cardioaccelerator effects of gamma MSH and related peptides.

We have recently demonstrated that the hypertensinogenic and natriuretic actions of ACTHI-39 can be found in a non-steroidogenic fragment of ACTH, ACTH4-10. These effects of ACTH or ACTH4-10 may be due to their ability to act as weak agonists of gamma MSH. gamma MSH is found in the 16K N-terminus of pro-opiocortin, and contains a sequence analogous to ACTH4-10, gamma MSH3-9. We investigated the cardiovascular effects of gamma 2MSH, gamma MSH3-9, and sterically restricted analogs of ACTH4-10. The results indicate that gamma MSH3-9, had essentially the same activities as ACTH4-10. The addition of five other amino acid residues to gamma MSH3-9 (gamma 2MSH) resulted in significant enhancement of pressor and cardioaccelerator activity. Steric restriction of the ACTH4-10 sequence by the substitution of a D-Phe in place of an L-Phe residue in position #7, or cyclization of the peptide by a half-Cys4, half Cys10 intramolecular disulfide-bridge derivatization, resulted in increased cardiovascular activities. Based on these data, the cardiovascular actions of ACTH4-10, gamma MSH3-9, and gamma 2MSH are predicted to be due to the assumption of a reverse-turn three-dimensional structure. The additional residues in gamma 2MSH appear to specifically enhance the cardiovascular activities of gamma MSH3-9. The results suggest the existence of a new class of hypophyseal peptides with cardiovascular activities, which require the assumption of a defined three-dimensional structure.

Adrenocorticotropic Hormone↗
PubMed1985

Gamma-2MSH is natriuretic in the rat.

Previous reports suggest that peptides containing an amino acid sequence similar to that of ACTH-(4-10) increased Na excretion in the rat. gamma 2MSH contains such a sequence. An in vivo rat bioassay for natriuretic factors was employed to demonstrate the natriuretic action of gamma 2MSH. A significant natriuretic effect was observed, with a peak response 30-50 min following the bolus injections of 0.64, 6.4 or 64 pmol, but not with smaller or larger amounts of gamma 2MSH. A kaliuretic and diuretic action of gamma 2MSH was not consistently evident. gamma MSH may represent an endogenous compound involved in the physiological regulation of Na excretion.

Animals↗
PubMed1985

Cardiovascular investigations of an endogenous digoxin-like factor.

A circulating factor with digoxin immunoreactivity has been demonstrated. Elevated levels of this substance appear to be present after volume expansion and salt loading, and in some forms of hypertension. The potentially causative role for this factor in hypertension can be demonstrated by the normalization of blood pressure after antidigoxin antibody infusions in low-renin and sodium-dependent hypertension. The possibility that renal excretory defects may be the initiating event to elevate endogenous digoxin is suggested by studies with normotensive humans and monkeys with renal disease. In the latter case cardiovascular deficits were noted that were analogous to those detected in renal hypertensive monkeys with elevated endogenous digoxin. Considered together, these results suggest the existence of a natriuretic and hypertensive substance that plays a role in body fluid homeostasis and blood pressure regulation.

Animals↗
PubMed1985

Natriuretic peptides derived from pro-opiocortin.

Natriuresis in response to hypertonicity, volume loads, or high sodium diets has been proposed to be mediated by the release of a humoral factor(s), and controlled by the central nervous system. We have determined that the natriuretic activity of ACTH or alpha MSH resides in a common sequence, ACTH(4-10)/alpha MSH(4-10). Steric restriction of this peptide by replacement of an L-Phe residue with a D-Phe produced a superagonist. Gamma-2 MSH is a peptide derived from the 16K N-terminus of pro-opiocortin, which contains an ACTH(4-10)-like sequence. The natriuretic effect of gamma-2 MSH was maximal between 0.64 pmole to 64 pmole. Doses greater than 128 pmole produced no significant effects on renal sodium excretion. The regulated release of gamma MSH peptides may contribute to CNS regulation of renal sodium excretion.

Adrenocorticotropic Hormone↗
PubMed1984

Varying the duration of A23187 administration alters its effect on adrenal steroidogenesis.

A variety of effects of A23187 have been reported as its actions on adrenocortical steroidogenesis. This diversity probably resulted because of differences in the protocol of applying the Ca++ ionophore. We continue to observe a dose-dependent potentiation by the ionophore on ACTH-stimulated corticosterone secretory activity of superfused rat adrenocortical slices. This effect was eliminated or reversed if the tissue was pretreated with A23187 for 30 min prior to secretagogue application. The quality of the ionophore effect also depends on the submaximal dose of ACTH employed.

Adrenal Cortex↗
PubMed1984

Prolactin stimulates and potentiates adrenal steroid secretion in vitro.

Prolactin, alone and in combination with ACTH, was tested for its ability to release steroids from rat adrenocortical slices superfused in vitro. The hormone possessed weak activity alone (minimal responsive dose = 1 U), but was able to potentiate the ACTH-stimulated corticoid release at much lower doses (significant response over ACTH alone at 0.01 U prolactin). This latter dosage was calculated to be within the physiologic range of prolactin in blood. Analysis of individual steroids in superfusate by RIA revealed that aldosterone release was most sensitive to prolactin, followed by corticosterone, androstenedione, and progesterone. We conclude that prolactin is an adrenocortical secretagogue of physiological relevance in the rat, and that it could play a role in enhancing the action of ACTH to acutely release steroids.

Adrenal Cortex↗
PubMed1983

Naloxone potentiates ACTH and angiotension II but not potassium stimulated aldosterone secretion, in vitro.

The effects of naloxone on basal and ACTH, Angiotensin II (AII) and [K+] o stimulated aldosterone secretion from superfused rat adrenocortical tissue were investigated. A high dose (10(-6) M) of naloxone inhibited while a smaller dose (10(-10) M) potentiated and doses of 10(-8) or 10(-12) M naloxone were without an effect on ACTH stimulated aldosterone secretion. A potentiation of AII stimulated aldosterone secretion was observed beginning 2 hrs after 10(-6) or 10(-10) M naloxone was administered while no effect was observed with 10(-4) M naloxone. No effects of 10(-6), 10(-8), 10(-12) M naloxone were detected on aldosterone secretion stimulated by transiently elevating extracellular potassium. Naloxone from 10(-4) to 10(-12) M did not appear to significantly influence basal steroidogenic activity under these conditions. These findings demonstrate that the "opioid antagonist" naloxone has prominent actions on adrenocortical tissue. Both the specificity and lack of specificity of the action of this agent to influence the activity of the 3 secretagogues suggest that naloxone and possibly a naturally occurring endogenous ligand interacts with one or more membrane receptor distinct from the ACTH receptor. A naturally occurring ligand for this receptor could play a prominent role in the physiological regulation of adrenal steroid secretion.

Adrenal Cortex↗
PubMed1983

60-Hz electric field alters the steroidogenic response of rat adrenal tissue, in vitro.

Exposure to a 60-Hz electric field at 10 kV/m but not at 5 kV/m, 100 kV/m or 1000 kV/m caused a highly significant, threefold elevation in the steroidogenic response of rat adrenal cortical tissue after the administration of 10 mU of adrenocorticotrophic hormone (ACTH) under in vitro, superfusion conditions. A 60-Hz electric field can directly influence the function of mammalian tissue in the absence of central-nervous-system mediation.

Adrenal Cortex↗
PubMed1982

Membrane potential changes of mouse adrenal zona fasciculata cells in response to adrenocorticotropin and adenosine 3',5'-monophosphate.

ACTH superfused onto mouse adrenal zona fasciculata tissue caused a transient, dose-dependent membrane depolarization. The log of the dose of ACTH was linearly related to the magnitude of depolarization. The onset of depolarization was rapid and dose dependent. Resting membrane potential changes observed after ACTH were blocked by CoCl2 but not tetrodotoxin or 4-aminopyridine, indicating that these depolarizations were dependent primarily on transmembrane Ca++ flux. CoCl2 also significantly blocked ACTH-stimulated adrenal steroid production; 4-aminopyridine had a much smaller and greatly delayed effect, whereas tetrodotoxin had no detectable effect on steroidogenesis. cAMP administration to adrenal zona fasciculata cells elicited transient, dose-dependent membrane depolarizations, which closely resembled those observed after ACTH treatment. In contrast to ACTH, CoCl2 did not block the cAMP-induced depolarization. These and other studies indicate that ACTH initiates a complex series of events by which steroidogenesis is stimulated. One mechanism may involve a change in membrane permeability to Ca++ independently of cAMP generation; a second mechanism may involve the activation of adenylate cyclase which subsequently influences the membrane conductance of the fasciculata cell membrane.

4-Aminopyridine↗
PubMed1981

Effects of extracellular potassium and 4-aminopyridine on corticosteroid secretion.

Transient alteration in [K+]0 significantly influenced basal and stimulated corticosteroid secretory activity of superfused rat adrenal cortical tissue slices. A transient rise in [K%]0 resulted in an increase in basal steroid secretion. Removal of extracellular K+ from the superfusing medium significantly reduced basal as well as ACTh and cAMP-stimulated steroid production. Elevated [K+0] significantly potentiated cAMP's and to a much lesser extent increased ACTH's steroid stimulatory activity. The K+ flux inhibitor, 4-aminopyridine (4AP) (10 mM) elicited an initial decline in basal steroid secretory activity. A single 10-ml dose of 10 mM but not 1 mM 4AP significantly diminished, for many hours, ACTH's and cAMP's ability to stimulate adrenal steroid secretion. The combination of elevated [K+]0 and 4AP administration resulted in additional reduction of the ability of ACTH to stimulate steroid production. This combination of 4AP with [K+]0 elevations also blocked the potentiating effect of K+ on cAMP-stimulated steroid secretion. Together these findings demonstrated that some procedures which can alter the distribution of K+ across the adrenal cell membrane are capable of profoundly influencing the secretion of the predominant glucocorticoid from the rat adrenal gland under in vitro superfusion conditions. The data support the suggestion that a slight rise in intracellular K+ concentration would be stimulatory and that further increase of, or a decline in, this ion's intracellular level would be inhibitory to basal and stimulated steroid secretory activity.

Adrenal Cortex↗
PubMed1980

Adrenocorticotrophic hormone and cyclic adenosine monophosphate effect on mouse adrenal cortical cell membrane potential.

Adrenocorticotrophic hormone (ACTH) and cyclic adenosine monophosphate (cAMP) both caused a rapid and transient depolarization of the resulting membrane potential of superfused rat adrenal cortical cells. The membrane depolarization to both secretagogues were very similar. The membrane potential changes occurred as early as 0.1 min and were dose dependent in both onset and extent of depolarization.

Adrenal Cortex↗