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Biomedical subjects

G S Roth

Publications and source records attributed to G S Roth.

At least 145 records · Page 8Linked to original sources
PubMed1989

Decreased signal transduction in rat parotid cell aggregates during aging is not due to loss of alpha 1-adrenergic receptors.

Specific binding of the agonist, 3H-epinephrine, and antagonist, 3H-prazosin, to alpha 1-adrenergic receptors in both intact and broken rat parotid cell preparations was measured as a function of age in Wistar rats. Agonist binding exhibited approximately tenfold weaker affinity (Kd approximately 10 nM) for both intact and broken cells than did the antagonist (Kd approximately 1 nM). In addition, Bmax for the agonist was only 25 to 50% of that of the antagonist (7-10 fmol/mg protein vs. 15-30 fmol/mg protein) in both preparations. Binding affinity decreased significantly between ages 3 and 24 months for the antagonist but not the agonist in both intact and broken cells. The number of binding sites did not change with age in intact cells when measured with either agonist or antagonist, or when measured with agonist in broken cells, but increased markedly (approximately two fold) with age in broken cells for the antagonist. The latter results support the hypothesis that the aged rat parotid cell exhibits a naturally occurring, post-alpha 1-adrenoreceptor defect in signal transduction.

Aging↗
PubMed1989

Promotion of wound repair in old mice by local injection of macrophages.

Application of peritoneal macrophages to experimentally induced cutaneous wounds of old mice accelerates healing to levels almost comparable to those of untreated young animals. Slightly greater acceleration is observed when macrophages are obtained from young as opposed to old donors. These findings are consistent with a defect in macrophage function as a cause of impaired wound healing in senescence and suggest a possible therapeutic strategy.

Aging↗
PubMed1989

Impaired down-regulation of pituitary dopamine receptors by estradiol in aged rats.

Administration of 17 beta-estradiol to mature (6-12 months) rats results in a more than 50% reduction in pituitary dopamine receptor concentrations, without affecting binding affinity. In contrast, when the same manipulation is performed on senescent (24-25 months) rats, negligible change in receptor concentration occurs. These results suggest that age-related increases in estrogen-stimulated prolactin release are not due to decreased dopaminergic inhibition at the receptor level.

Aging↗
PubMed1988

Alterations in muscarinic control of striatal dopamine autoreceptors in senescence: a deficit at the ligand-muscarinic receptor interface?

Research has indicated that the release of striatal dopamine (DA) is controlled by inhibitory DA autoreceptors which are in turn regulated by inhibitory muscarinic inhibitory cholinergic heteroreceptors (HTRs) located in close vicinity to the autoreceptors. Muscarinic activation enhances K+-evoked release of DA from striatal slices from mature but not senescent rats. Since it has been shown that age-dependent declines in Ca2+ mediated acetylcholine release can be restored by the ionophore A23187, it was of interest to determine if age-related decrements in Ca2+ mobilization might contribute to the alterations in muscarinic control of the striatal DA autoreceptors seen in senescence. Cross-cut striatal tissue slices obtained from two age-groups (6 and 24 months) of Wistar rats were superfused with a modified Krebs-Ringer medium containing 2.5 mM KCl. After a 30-min equilibration period, a 5-min baseline fraction was collected. The medium was then switched to one which contained 30 mM KCl and, depending upon the experiment, the muscarinic agonists carbachol, or oxotremorine or the Ca2+ mobilizing agents A23187 or inositoltrisphosphate (IP3) and enhancement of K+-evoked release of DA was examined. Six 5-min fractions were collected. DA release was determined by HPLC coupled to electrochemical detection. Results indicated that although deficits were seen in oxotremorine and carbachol enhancement of K+-evoked release of DA, these decrements were not observed when either A23187 or IP3 were utilized to enhance the K+-evoked release of DA.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

Age-related impairment in rat parotid cell alpha 1-adrenergic action at the level of inositol trisphosphate responsiveness.

Alpha 1-Adrenergic-stimulated calcium efflux from rat parotid cell aggregates declines approx. 40% between 3 and 24 months of age, with the bulk of the reduction occurring between 12 and 24 months. Intracellular free calcium levels following alpha 1-adrenoceptor stimulation are also reduced about 40% between 3 and 24 months. No significant age differences in stimulation of inositol mono-, bis- or trisphosphate production are observed. However, the ability of inositol trisphosphate to directly stimulate calcium efflux is reduced by about 50% with increasing age. Concentrations of this inositol phosphate required for maximal calcium release do not change between 3 and 24 months. Differences in response are not due to a reduction in uptake of inositol trisphosphate into older cells, but suggest an age-related defect in the ability of inositol trisphosphate to liberate calcium from intracellular stores. Such dysfunction may be at least partially responsible for impaired alpha 1-adrenergic responsiveness during aging.

Age Factors↗
PubMed1988

Modification of ATP-dependent Ca2+ transport in rat parotid basolateral membranes during aging.

Previous experiments have shown that senescent rat parotid acinar cells display marked reductions in Ca2+ release following alpha 1-adrenoreceptor stimulation. We report here, that in this naturally occurring perturbation of exocrine secretion, ATP-dependent Ca2+ transport in the parotid basolateral plasma membrane, the principal Ca2+ extrusion pathway in the parotid, is also modified. ATP-dependent Ca2+ transport in membrane vesicles isolated from senescent rats (approx. 24 months) is decreased approximately 30-50% as compared to that in vesicles isolated from younger rats (approx. 4 months). This alteration in Ca2+ pump activity is not due to (i) non-specific effects of vesicle preparation in the two animal groups, (ii) increased leakiness to Ca2+, or (iii) any apparent alteration in permeability of the membrane to K+ and Cl-. Kinetic studies demonstrate that the ATP-dependent Ca2+ transport activity in vesicles from senescent rats has similar maximal velocity to that of vesicles from young adult rats (27 vs. 31 nmol Ca2+/mg protein per min), however, it exhibits an approximately 50% increase in Km for Ca2+ (91 nM vs. 60 nM). Cytosolic free Ca2+, measured by Quin 2 fluorescence, in parotid acini following alpha 1-adrenoreceptor stimulation was much less elevated in preparations from senescent rats. These results may account, at least in part, for the previously reported physiological alteration in Ca2+ efflux seen in senescent rat parotid cells.

Adenosine Triphosphate↗
PubMed1988

Mechanisms of altered hormone and neurotransmitter action during aging: the role of impaired calcium mobilization.

Age-related changes in hormone and neurotransmitter regulation of physiological functions result from various mechanistic alterations. In many cases changes in the receptors for these agents appear to be closely linked to altered responsiveness. In other instances, receptors are unaffected by aging, and various post-receptor changes result in functional deterioration. Examples of the latter situation include stimulation of cyclic AMP production and high-affinity association of steroid receptor-hormone complexes with nuclear acceptor sites in various cell and tissue types. One of the most noteworthy post-receptor changes appears to be an impaired ability to stimulate calcium mobilization in many aged systems resulting in reductions in various biological responses. Although the processes which govern regulation of calcium fluxes vary with cell type, many such dysfunctions can be at least partially reversed if sufficient calcium can be transported to appropriate cellular sites. Thus, elucidation of the molecular mechanisms involved in impaired calcium mobilization may provide the basis for new therapeutic strategies.

Aging↗
PubMed1987

Effects of aging on parathyroid hormone stimulated ionic fluxes in rat parotid cell aggregates.

The effects of aging on parathyroid hormone stimulated calcium and phosphate efflux from isolated rat parotid cell aggregates differed from that of epinephrine stimulated calcium efflux in magnitude, chronology, and ionic dependence. Parathyroid stimulated ionic fluxes were maximal at 1-3 months of age, declined until 12 months and remained constant thereafter. Epinephrine stimulated calcium efflux remained maximal between 3 and 12 months and declined until at least 24 months. Absolute stimulation of calcium efflux over basal levels was maximal at 4-8% while phosphate efflux was 20-30%.

Aging↗
PubMed1987

Effect of aging on striatal dopamine receptor subtype recovery following N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline blockade and relation to motor function in Wistar rats.

Recovery of D1- and D2-dopamine receptors in Wistar rat corpora striata were assessed following N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ blockade). Absolute recovery declines during senescence approximately 25 and 40% for the D1- and D2-subtypes, respectively. Net biosynthetic reductions are comparable to the overall age-related decreases in receptor concentrations for this rat strain. EEDQ administration also induces catalepsy behavior and impairs ability of animals to remain on an inclined screen. Recovery of inclined screen performance is also reduced with age, but is not strictly proportional to recovery of receptor concentrations.

Aging↗
PubMed1987

Wound repair in mice as influenced by age and antimacrophage serum.

The closure of bilateral, full-thickness cutaneous wounds made over the back with a sharp paper punch was measured with calipers and assessed histologically in C57BL/6J male mice for 10 days after wounding. Young (6 months) mice exhibited a significantly more rapid rate of wound closure and repair than did mature (15 months) or aged (26 or 27 months) mice. The repair rate in mature and aged mice did not differ. Young mice, injected subcutaneously at the wound sites with rabbit antimouse macrophage serum (RAMMS) 5 min before wounding and on days 1 and 3 after wounding, exhibited slow delayed closure of cutaneous wounds during days 1 to 4 after wounding, similar to that of untreated aged mice. The early closure rate of mice injected with normal rabbit serum or physiological saline was rapid, resembling that of untreated young mice. The results suggest that cutaneous wound repair in mice is another physiological phenomenon whose rate of change is age related, but not necessarily progressive to senescence. The results also imply that macrophage functional decline may contribute to the slowing of wound repair in middle-aged and aged mice compared to young mice.

Aging↗
PubMed1987

Accelerated wound repair in old deer mice (Peromyscus maniculatus) and white-footed mice (Peromyscus leucopus).

The closure of bilateral full thickness cutaneous wounds, made over the back with a sharp paper punch, was measured and assessed histologically in outbred deer mice (Peromyscus maniculatus) and white-footed mice (Peromyscus leucopus). In contrast to inbred C57BL/6J laboratory mice (Mus musculus), in which the rate of wound repair was more rapid in young than in mature or aged mice (Cohen et al., 1987), wound repair in Peromyscus was most rapid in aged animals. Aged Peromyscus (45 to 70 months) achieved 50% closure of cutaneous wounds within 3 to 4 days, whereas mature (23 or 24 months) and young Peromyscus required 5 to 7.7 days to reach the 50% closure level. Histologic indices were compatible with the more rapid rate of closure of the cutaneous wounds in aged Peromyscus. The reasons for the unexpected increase in the rate of wound repair with increasing age in Peromyscus are not clear but stress-related hormonal and cellular factors may play an important role.

Aging↗
PubMed1987

Ionophore A23187 partially reverses LH secretory defect of pituitary cells from old rats.

We measured in vitro release of luteinizing hormone (LH) in the presence of 1.5 mM extracellular calcium, with and without LH-releasing hormone (LHRH; 10(-10) to 10(-7) M) or the ionophore A23187 (10(-7) to 10(-4) M), in primary cultures of anterior pituitary cells from intact mature (6 mo) and old (24 mo) male and intact and ovariectomized mature and old female Wistar rats. Base-line as well as LHRH- and A23187-mediated LH secretion was decreased from cells of old rats. However, exposure to A23187 led to a nearly twofold greater augmentation of LH release from cells of old rats, thus decreasing the apparent age-related LH secretory deficit by approximately one-half. We then measured LHRH-mediated (10(-8) M) vs. A23187-mediated (10(-4) M) LH release with and without extracellular calcium (0.08-1.5 mM). For cells from both mature and old rats, there was a similar calcium dependency for A23187- and LHRH-mediated LH release, with optimal LH secretion at 1.0-1.5 mM extracellular calcium concentrations. Again, both LHRH- and A23187-stimulated LH release was significantly lower and exposure to A23187 led to a greater increase in LH release from cells of old rats. Taken together with similar findings in other systems, these data suggest that the in vitro LH secretory defect of pituitary cells from old rats results in part from one or more defects in calcium mobilization and that such alterations may be a widespread manifestation of aging.

Aging↗
PubMed1986

Modulation of rat striatal membrane fluidity: effects on age related differences in dopamine receptor concentrations.

Rat striatal membrane fluidity and dopamine receptor concentrations were modulated in vitro by ethanol or cholesterol hemisuccinate treatment. In general, available receptor levels are directly proportional to membrane fluidity. However, receptor concentrations remained higher in mature membranes at all levels of fluidity attained. These results suggest that apparent loss of striatal dopamine receptors during aging is not due to membrane sequestration.

Aging↗
PubMed1986

Altered estrogen action in the senescent rat uterus: a model for steroid resistance during aging.

The estrogen stimulated rat uterus serves as a useful model to examine steroid resistance during aging. This system exhibits receptor loss, impaired stimulation of RNA polymerase II and defects in nuclear translocation (or enhanced association) of receptor-estradiol complexes. All of these defects appear to contribute in part to decreased estrogen responsiveness of the senescent rodent uterus.

Aging↗