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Biomedical subjects

G S Roth

Publications and source records attributed to G S Roth.

At least 181 records · Page 10Linked to original sources
PubMed1983

Stimulation of parotid cell glucose oxidation. Role of alpha 1-adrenergic receptors and calcium mobilization.

Epinephrine stimulated glucose oxidation in isolated rat parotid cell aggregates through alpha- and beta-adrenergic mechanisms. The alpha-adrenergic component appeared to be of the alpha 1-receptor subtype as evidenced by inhibition studies with selective antagonists. Calcium mobilization in the presence of the ionophore A23187 was as capable as epinephrine in eliciting this response. Epinephrine stimulation of glucose oxidation was, however, only partially dependent on extracellular calcium. Only the upper 50% of the maximal (10(-5) M) epinephrine response required external calcium, since stimulation by 10(-6) M epinephrine, which elicits only about 40% of the maximal (10(-5) M epinephrine) response, was independent of external calcium. Furthermore, no external calcium dependence was observed for pure alpha- or beta-adrenergic stimulation alone, which comprised about 60 and 40%, respectively, of the maximal epinephrine response. Thus, adrenergic mediated parotid cell glucose oxidation may proceed by different mechanisms depending on the extent and nature of cellular stimulation.

Adrenergic alpha-Antagonists↗
PubMed1983

Effect of aging on prolactin regulation of rat striatal dopamine receptor concentrations.

Administration of highly purified rat prolactin by miniosmotic pump increases striatal dopamine receptor concentrations in both mature (4-6 months) and senescent (24 months) male Wistar rats. Although receptor levels in untreated rats are about 30% lower in the senescent group, elevated levels following prolactin are not significantly different between ages. Increases in circulating prolactin levels after 7 days of treatment were not detectable at the low concentrations used (150 ng/hr). In fact, there was a trend toward decreases in circulating prolactin concentrations to the same level in both groups after treatment, despite substantially elevated basal levels in many of the senescent rats.

Aging↗
PubMed1983

Multiple transduction mechanisms are likely involved in calcium-mediated exocrine secretory events in rat parotid cells.

The parotid gland of the aged rat provides an example of an altered alpha 1-adrenergic physiologic response (K+ efflux) resulting from a postreceptor perturbation in signal transduction mechanisms (Ito, H., Baum, B. J., Uchida, T., Hoopes, M. T., Bodner, L. & Roth, G. S. (1982) J. Biol. Chem. 257, 9532-9538). This alteration in gland function can be completely circumvented by eliciting K+ efflux via the Ca2+-ionophore, A23187, at several Ca2+ concentrations (ibid.). Since Ca2+ is purported to mediate other secretory events in the rat parotid, we have probed neurotransmitter regulated Ca2+ mobilization and secretory mechanisms in this tissue by employing an aging paradigm. The responses studied were alpha-adrenergic- and muscarinic-cholinergic-mediated K+ efflux, 45Ca2+ release, and amylase secretion. No differences were detected between young (3 months) and old (24 months) cell preparations for any muscarinic-cholinergic agonist-induced response studied. Following alpha-adrenergic stimulation, K+ efflux and 45Ca2+ release from old cell preparations were reduced markedly, while no changes were found for the amylase secretion response. These results suggest that 1) alpha-adrenergic and cholinergic signal transduction mechanisms for K+ efflux and 45Ca2+ release are dissociated in cells of the rat parotid gland, and 2) following alpha 1-adrenergic stimulation, signal transduction likely proceeds by at least two pathways, one which is apparently involved in protein excytosis (intact in cells from old rats) and the other which is apparently involved in K+ efflux and 45Ca2+ release (perturbed in old cells).

Aging↗
PubMed1983

Life-long dietary restriction affects striatally-mediated behavioral responses in aged rats.

The effects of life-long dietary restriction on rotational behavior and stereotypy induced by intrastriatally administered dopamine-excitatory (dopamine, DA; amphetamine, AMPH) or cholinergic inhibitory (atropine, AT) agents were examined in rats. Three groups of male Wistar rats were used; mature ad lib (YAL, 6 month), old ad lib (OAL 24 month), and old restricted animals (OR). OR animals were fed and fasted on alternate days from weaning. Each rat was unilaterally lesioned in the left substantia nigra with 6-hydroxydopamine and a cannula was implanted in the right caudate nucleus. Several doses of each drug [AT (0, 1, 7, micrograms) DA (0, 5, 50 micrograms), and AMPH (0, 2, 5, 5, 10 micrograms)] were given randomly (1 dose/day with 1 week between drugs). All doses of a particular drug were given before the next drug regimen was started. A combination of AMPH (25 micrograms) and AT (1 microgram) was also administered in one injection at the completion of all other regimens. Results showed that OR animals responded as well as YAL animals and far better than OAL animals following AMPH, DA, or low doses of AT. However, both the high dose of AT and the combined dose of AMPH-AT seemed to suppress responding in OR animals. Neither AT alone or AMPH-AT combinations had effects in OAL animals. Results are discussed in terms of the possible specificity of effects of dietary restriction on striatal functioning and behavior in senescence.

Aging↗
PubMed1982

Loss of rat ventricular alpha 1-adrenergic receptors during aging.

Ventricular alpha 1-adrenergic receptor concentration, measured by specific binding of [3H]-prazosin, decreases by 33% as rats age from 3 to 24 months. No age changes occur in binding affinity for [3H]-prazosin or potency of various alpha-adrenergic agonists and antagonists to displace [3H]-prazosin. The ratio of membrane protein to ventricular wet weight also does not change significantly with age. These results suggest a possible mechanism for loss of cardiovascular alpha-adrenergic responsiveness during aging.

Aging↗
PubMed1982

Modulation of rat parotid cell alpha-adrenergic responsiveness at a step subsequent to receptor activation.

Parotid gland acinar cells, prepared from 12- and 24-month-old rats, show decreased physiological responsiveness to alpha-adrenergic stimulation in vitro compared to cells from 3-month-old rats. K+ efflux, an index of water and electrolyte secretion, was approximately 35% lower with 12- and 24-month-old parotid cells. No loss of alpha-adrenergic receptors, their binding affinity for specific alpha-adrenergic ligands, or their relative subtype distribution, accompanied the diminished exocrine function. Conversely, a significant reduction in alpha-adrenergic-mediated phospholipid turnover in, and 45Ca2+ efflux from, parotid cells of older rats was observed. These changes in phospholipid metabolism and Ca2+ flux were parallel to changes seen in K+ efflux as judged by dose-response studies. When the alpha-adrenergic receptor was by-passed by using the Ca2+-ionophore A-23187 to elicit K+ efflux, young and old parotid cells were equally responsive. In aggregate the findings suggest that parotid gland cells from older rats display an altered alpha-adrenergic signal transduction mechanism at a site between the receptor and phospholipid turnover/Ca2+ mobilization.

Aging↗
PubMed1982

K+ release from rat parotid cells: an alpha 1-adrenergic mediated event.

To characterize alpha-adrenergic receptors in rat parotid gland tissue, 9,10-[9,10-3H(N)]-dihydro-alpha-ergocryptine ([3H]DHE) and [3H]prazosin binding to membranes and stimulated K+ release from parotid cell aggregates were examined. Prazosin (selective alpha 1-adrenergic antagonist), displacement of [3H]DHE binding from parotid membranes was biphasic, indicating the presence of both alpha 1- and alpha 2-adrenergic receptors. The numbers of alpha 1- and alpha 2-receptors were about equal. alpha 1-Adrenergic receptors were further studied by [3H]prazosin binding. [3H]Prazosin binding was a rapid, reversible, saturable and stereospecific process, with high affinity (KD = 0.38 nM) and low capacity (Bmax = 380 fmoles ligand bound/g tissue, 10.1 fmoles/mg protein) as determined by Scatchard analysis. The characteristics of [3H]prazosin binding were in good agreement with those of catecholamine-stimulated K+ release, suggesting that K+ release from rat parotid gland cells is an alpha 1-adrenergic mediated effect.

Animals↗
PubMed1982

Changes in the mechanisms of hormone and neurotransmitter action during aging: current status of the role of receptor and post-receptor alterations. A review.

Alterations in responsiveness to hormones and neurotransmitters during aging appear to be due to changes at both the receptor and post-receptor levels. Although many such observations have now been independently confirmed, disagreement over the extent and/or importance of receptor alterations exists in a number of cases. Receptors do not appear to change with age in certain systems, but only a few reports have actually been able to localize particular post-receptor alterations responsible for changes in response. This review attempts to catalogue studies in these areas which have been carried out to date, and discusses possible reasons for discrepancies as well as future research directions.

Adult↗
PubMed1982

Alpha1-adrenergic stimulation of phosphatidylinositol-phosphatidic acid turnover in rat parotid cells.

The regulation of phosphatidylinositol turnover by alpha-adrenergic agonists in rat parotid acinar cell aggregates was examined with respect to kinetics and agonist-antagonist interactions. Phosphatidylinositol turnover was followed by the changes in the specific activities of [32P]phosphatidic acid and [32P]phosphatidylinositol. The specific activity of phosphatidic acid increased rapidly (within 1 min) after addition of epinephrine (10(-5) M), reached a maximal level within 12-16 min, and then decreased. Incorporation of 32P into phosphatidylinositol exhibited a lag phase of about 5 min and then increased continuously for an additional 40 min. The absolute amounts of phosphatidic acid and phosphatidylinositol did not change. The concentrations of epinephrine needed to stimulate 32P incorporation into phosphatidic acid and phosphatidylinositol, measured at 15 and 30 min, respectively, were similar; Ka values of 2.05 +/- 0.46 X 10(-6) M for phosphatidic acid and 2.98 +/- 0.30 X 10(-6) M for phosphatidylinositol were found. The effects of agonists on 32P labeling of phosphatidylinositol, in order of potency, were epinephrine greater than or equal to norepinephrine greater than phenylephrine much greater than normetanephrine. When various adrenergic antagonists were evaluated for their ability to inhibit 10(-5) M epinephrine-stimulated 32P incorporation into both phosphatidic acid and phosphatidylinositol, the order of antagonist potency was prazosin greater than or equal to phenoxybenzamine greater than phentolamine greater than or equal to yohimbine greater than much greater than propranolol. These findings indicate that phosphatidylinositol-phosphatidic acid turnover in the rat parotid gland is mediated by the alpha 1-adrenergic receptor system.

Adrenergic alpha-Agonists↗
PubMed1981

Dietary restriction retards the age-associated loss of rat striatal dopaminergic receptors.

In male Wistar rats subjected to dietary restriction by alternate days of feeding and fasting the normal age-associated loss of striatal dopamine receptors in the brain was substantially retarded. The mean survival time of the rats on the restricted diet was increased by approximately 40 percent compared to control rats given free access to food. Dopamine receptor concentrations in striata of 24-month-old rats that had been on a restricted diet since weaning were 50 percent higher than those of control animals of the same age, and essentially comparable to 3- and 6-month-old control rats.

Aging↗
PubMed1981

beta-Adrenergic regulation of protein phosphorylation and its relationship to exocrine secretion in dispersed rat parotid gland acinar cells.

The possible role of cyclic AMP-mediated phosphorylation events in the regulation of exocrine secretion after beta-adrenergic stimulation was examined in vitro in dispersed acinar cell aggregates from rat parotid gland. l-Isoproterenol, a beta-adrenergic agonist, stimulated endogenous activity of cyclic AMP-dependent protein kinase, alterations in the 32P content of 3 parotid phosphoproteins (increased 32P in 2, Mr = 27,000 and 14,000; decreased 32P in the remaining, Mr = 13,600), and amylase secretion in a dose-dependent manner. All responses were half-maximal within a range of l-isoproterenol concentrations of approximately 4 X 10(-8) to 5 X 10(-7) M. Examination of the time course of these 3 processes revealed that by 30 s after addition of l-isoproterenol, significant elevations in cyclic AMP-dependent protein kinase activity and alterations in the 32P content of the 3 parotid proteins had occurred, whereas secretion of amylase from cells was first detected 1-2 1/2 min after hormonal stimulation. Dibutyryl cyclic AMP (2 mM) elicited the same changes in parotid protein 32P content as l-isoproterenol. Our results support the concept of a role for cyclic AMP-regulated protein phosphorylation in the sequence of cellular events leading to exocrine protein secretion from the rat parotid gland following beta-adrenergic stimulation.

Animals↗
PubMed1981

Effects of thyroid hormones on cardiac hypertrophy and beta-adrenergic receptors during aging.

Administration of thyroxine daily at a dosage of 6.4 mu g/g body weight stimulates cardiac hypertrophy in both 9--13-month-old (mature, n = 34) and 22--24-month-old (senescent, n = 45) Wistar rats. The increase due to thyroxine as well as the time course of the effect do not change with age, although ventricular wet weight to tibial length ratios are higher in senescent animals at 0, 3, and 7 days of treatment (senescent controls = 0.331; senescent hypertrophied = 0.395; mature controls = 0.295; mature hypertrophied = 0.336). Hypertrophy is maximal after 3 days. beta-Adrenergic receptor levels as measured by stereospecific binding of dihydroalprenolol in mature rats are increased about two-fold after 7 days of thyroxine treatment (mature controls = 35 +/- 3 fmol/mg protein, mature treated = 65 +/- 6 fmol/mg protein). Although both stimulated and control values do not differ significantly between mature and senescent groups (senescent controls = 45 +/- 4 fmol/mg protein, senescent treated = 56 +/- 9 fmol/mg protein), the effect of thyroxine on senescent hearts is not statistically significant. In addition, 3-day levels do not increase over 0-day controls at either age. No significant differences in either beta-adrenergic receptor concentrations or affinities between age groups are observed at 0, 3, and 7 days of treatment. However, senescent membrane preparations contain 33% more sialic acid (a rough plasma membrane marker) per unit of protein than mature preparations. Thus, the beta-adrenergic receptor density per unit of sialic acid may be reduced very slightly in the senescent hearts.

Aging↗
PubMed1981

Beta-adrenergic regulation of rat parotid gland exocrine protein secretion during aging.

beta-Adrenergic regulation of exocrine protein secretion from the parotid gland was studied over the adult rat life span. Enzymatically dispersed cell aggregates were prepared from 3-, 6-, 12-, and 24-month-old rats and exocrine protein secretion (amylase release) measured. No age differences were seen in the time course of amylase release following (-)-isoproterenol stimulation or in the (-)-isoproterenol dose-response curve. the beta-adrenergic antagonist (+/-)-propanolol inhibited (-)-isoproterenol-stimulated protein secretion from parotid cell aggregates of young and old animals equally. Similarly dibutyryl cyclic AMP induced comparable rates of protein secretion from cells of different aged rats. Direct examination of beta-adrenergic receptor characteristics in parotid gland membranes from 3- to 24-month-old rats revealed no differences in the equilibrium dissociation constant (Kd) or maximum specific ligand binding capacity (receptor number). These results suggest that the rat parotid beta-adrenergic system remains functionally intact throughout the animals' lifetime.

Aging↗
PubMed1981

Effect of age on sensitivity to pain and brain opiate receptors.

Age-related differences in sensitivity to pain as induced by heat and electrical shock were seen among groups of rats; 2-3, 6-12, and 24 months of age. These are differences were at least partially obliterated by naloxone treatment, suggesting that changes may occur in the endogenous opioid system during aging. In contrast to higher pain thresholds in older animals, however, are decreased concentrations of opiate receptors in the frontal poles, striatum and hippocampus. Anterior cortex and amygdala exhibit a trend toward decreased concentration with increased age, but this is not significant. No age changes in binding affinity occur in any of the brain regions examined. Possible explanations for the apparent discrepancy between altered receptors and response include: higher endogenous opioid levels in aged rats, mediation of pain sensitivity by brain regions other than those examined, difficulties inherent in attempting to localize age changes at a single step in such a complex process, and possibly differential spinal pathways mediating the various types of pain.

Aging↗
PubMed1981

Biosynthetic rates of proteins having the characteristics of glucocorticoid receptors in adipocytes of mature and senescent rats.

An affinity chromatography technique has been utilized to compare the rates of putative glucocorticoid receptor biosynthesis in epididymal fat pad adipocytes of mature and senescent Wistar rats. Biosynthetic rates appear to be linear for at least 3 hours in both age groups, but are reduced by about one-half in the senescent cells. In contrast, incorporation of labeled amino acids into total protein is not altered with aging in this system. Thus, reduction in putative glucocorticoid receptor biosynthetic rate may reflect the effects of senescence on the expression of only a small part of the genome.

Aging↗