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Biomedical subjects

K A Gruber

Publications and source records attributed to K A Gruber.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

Ion transport characteristics in rhesus monkey erythrocytes: relationship to age and blood pressure.

Erythrocyte (RBC) ion transport characteristics were examined in six young Rhesus monkeys (RM) age 3.3 +/- .3 (means +/- S.D.) years and seven mature RM 15.4 +/- 1 (means +/- S.D.) years. It was found that the older RM when compared to the younger RM demonstrated significantly elevated mean arterial pressures (MAP) (96 +/- 15 versus 75 +/- 11 mmHg), RBC intracellular sodiums (RBC Nai) (16.2 +/- 4 versus 11 +/- 3 mEq/liter RBC) and NaK ATPase pump rates per RBC (PR) (PR = ouabain sensitive K uptake divided by ouabain binding sites per RBC) (104 +/- 18 versus 83 +/- 18 K+ ions/sec/pump unit). However, it was also found that when the data from both groups were pooled and collectively analyzed a significantly positive correlation could be found between MAP and RBC Nai (p less than .001, r = .82), MAP and PR (p less than .01, r = .67) as well as PR and RBC Nai (p less than .001, r = .76). The fact that positive correlations exist among these parameters, independent of age, would suggest that while MAP, RBC Nai and PR tend to be elevated with advancing age, these abberations are not invariable consequences of age and best reflect the pivotal abberration of rising Nai. While insufficient data exist to account for the rise in Nai and no cause-effect relationship can be established it is clear that rising MAP and PR correlate best with rising Nai.

Age Factors↗

Methods for investigating peptide precursors in the hypothalamus.

In conclusion, as in the aminergic nervous system, the hypothalamic neuropeptides "turn over" at a rate sufficient to maintain a "steady state" concentration within the hypothalamus. However, unlike catecholamine-secreting neurons, the brain peptides are synthesized and secreted by a much more circuitous mechanism, involving ribosomal biosynthesis as larger prohormones, axonal transport to the site of secretion, and enzymic processing to the biologically active hormones. The methods described here, including in vitro incubation and high-performance size-exclusion and reverse-phase chromatography, have been found to be useful for examining and comparing the rate and mechanism of biosynthesis of several hypothalamic neuropeptides.

Amino Acids↗

Preoptic-hypothalamic periventricular lesions reduce natriuresis to volume expansion.

The present experiment was designed to determine if electrolytic ablation of the periventricular tissue surrounding the anteroventral third ventricle (AV3V) altered the natriuresis typically seen during isotonic volume expansion. Control and AV3V-lesioned rats received intravenous infusions of 0.9% NaCl at 0.5 ml/min until 10% body weight was given. Arterial blood pressure was monitored, and urine was collected throughout the experiment. Following expansion, blood was processed for analysis of natriuretic hormonelike activity by chromatographic separation of plasma extracts followed by measuring antinatriferic activity across the isolated toad bladder. Urinary sodium excretion and urine volume during expansion were significantly less in rats with lesions surrounding the AV3V region than in control rats. Toad bladder bioassay showed a high level of natriuretic hormonelike activity in control animals following volume expansion, but no natriuretic hormonelike activity in plasma from volume-expanded rats with AV3V lesions. These data demonstrate that AV3V periventricular ablation attenuates the natriuresis induced by isotonic-volume expansion. In addition, preliminary results indicate the AV3V region may be a central site critical for natriuretic hormonelike activity and control of extracellular fluid volume.

Animals↗

Characterization of an inhibitor of granulocyte/monocyte colony formation in leukemic chicken plasma.

The plasma of chicks with myeloblastic leukemia (induced by avian myeloblastosis virus, AMV) contained an inhibitor which blocked colony formation in vitro by marrow cells. It eluted in the second protein peak obtained by Sephadex G-200 gel filtration and was found in the diafiltrate following defiltration through a UM 10 membrane under acidic conditions. It was not extractable with chloroform, was heat-stable (65 degrees C, 30 min), pronase-sensitive and had a molecular weight less than or equal to 5000 daltons as determined by high performance liquid chromatography. Thus, it appears to be a small, acid-soluble, heat-stable peptide. It had no interferon activity. It was not present or present only at very low levels in normal plasma. Furthermore, it was not elevated in chicks infected only with the nonleukemogenic helper virus of AMV, and was, therefore, associated with leukemia rather than virus-replication. Leukemic myeloblasts, purified by passage in suspension culture, released the inhibitor. It acted directly on the colony-forming cell and inhibited normal cells much more than leukemic cells. In normal marrow, macrophage and granulocyte progenitors were affected. A similar inhibitor in normal plasma inhibited only granulocyte progenitors.

Animals↗

Direct detection of the vasopressin precursor.

Cysteine-rich proteins were isolated from the hypothalamo-neurohypophyseal tract of dogs by high performance molecular weight chromatography. Trypsin digestion of these proteins produced a low molecular weight (LMW) peptide which was identified, by chemical and immunological assays, as (Arg8) vasopressin. There appear to be two forms of the precursor protein, one which has vasopressin immunoreactivity, and one which does not. Trypsin digestion of this latter protein produces high as well as LMW immunoreactivity. This suggests that the non-immunoreactive protein may be the precursor to the immunoreactive protein.

Animals↗

Vitamin A: not required for adrenal steroidogenesis in rats.

Previous work supporting the vitamin A dependency of adrenal function in rats neglected to take into account a secondary effect of the deficiency, a decrease in hepatic ascorbic acid biosynthesis. Vitamin A-depleted rats maintained on a diet free of ascorbate had a decrease in the activity of adrenal 3 beta-hydroxysteroid dehydrogenase, and extensive adrenocortical degeneration. The use of an ascorbate supplement prevented the symptoms. The results suggest that previous evidence for direct involvement of vitamin A in steroidogenesis may have been due to the production of a secondary deficiency, a chronic scorbutic condition.

Adrenal Glands↗