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G S Roth

Publications and source records attributed to G S Roth.

At least 109 records · Page 6Linked to original sources
PubMed1994

Effect of specific membrane perturbations on alpha 1-adrenergic and muscarinic-cholinergic signal transduction in rat parotid cell aggregates.

Alpha 1-adrenergic and muscarinic-cholinergic stimulated IP3 production and calcium mobilization are inhibited by treatment of parotid cell aggregates with methanol, hydrogen peroxide and saponin. Only methanol exerts an effect on binding to receptors. In most cases a close correspondence exists between inhibition of alpha 1-adrenergic and muscarini-cholinergic responses as well as inhibition of IP3 production and calcium mobilization. G-protein dependent signal transduction, therefore appears to be quite sensitive to plasma membrane perturbation and membrane active agents may provide useful tools for elucidation of transduction mechanisms and their regulation.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1994

Safety of prehospital nitroglycerin.

STUDY OBJECTIVE: To define changes in vital signs and cardiac rhythm in prehospital patients given sublingual nitroglycerin. DESIGN: A five-month prospective observational study with nitroglycerin administration as the independent variable. SETTING: Five independent advanced life support services. TYPE OF PARTICIPANT: Three hundred prehospital patients who were given nitroglycerin by advanced life support personnel for presumed myocardial ischemia or congestive heart failure; excluded were those without repeat vital signs or ECG monitoring and those given additional medications. INTERVENTION: Nitroglycerin was administered by regional emergency medical services protocols or by the order of an on-line medical command physician. RESULTS: Four study patients (1.3%) had adverse effects: One became asystolic and apneic for two minutes, two experienced profound bradycardia with hypotension, and one became hypotensive while tachycardic. All recovered. The 95% confidence interval for adverse effects was 0.5% to 3.4%. Mean fall in systolic blood pressure for the other 296 patients was 14 mm Hg for one dose (confidence interval, 11 to 16 mm Hg) and 8 mm Hg (confidence interval, 2 to 13 mm Hg) for a second dose. Heart rate changed minimally with nitroglycerin administration. The blood pressure drop was linearly correlated with initial systolic pressure (r = -.44; P < .001) but not correlated with number of prior doses of nitroglycerin, initial heart rate, advanced life support time interval, age, or sex. CONCLUSION: Nitroglycerin seems to be a relatively safe advanced life support drug; however, a few patients experience serious adverse effects. Most of the adverse effects we observed were bradycardic-hypotensive reactions, which appeared to be unpredictable by pretreatment characteristics. Emergency personnel should have an increased awareness of this danger when considering the use of prehospital nitroglycerin.

Administration, Sublingual↗
PubMed1994

Iron-56 irradiation diminishes muscarinic but not alpha 1-adrenergic-stimulated low-Km GTPase in rat brain.

Initial findings from our laboratory have indicated that muscarinic enhancement of K(+)-evoked release of dopamine from perifused striatal slices is reduced after exposure to 56Fe-particle irradiation. This finding suggested that there is a radiation-induced deficit in muscarinic receptor sensitivity. Subsequent findings have indicated that at least part of the loss in sensitivity may occur as a result of alterations in the initial steps of the signal transduction process and involve muscarinic receptor-G protein coupling/uncoupling. The present study was carried out to localize this deficit further by determining carbachol-stimulated low-Km guanosine triphosphatase (GTPase) activity in striatal and hippocampal tissue obtained from rats exposed to 0, 0.1 or 1.0 Gy of 56Fe-particle irradiation. In addition, to examine the specificity of the effect of 56Fe-particle irradiation, alpha 1-adrenergic-stimulated low-Km GTPase activity was also examined in these tissues. The results showed that there was a high degree of specificity in the effects of 56Fe particles. Decrements were observed in muscarinic-stimulated low-Km GTPase in striatum but not in hippocampus, and 56Fe-particle irradiation did not affect alpha 1-adrenergic low-Km GTPase activity in either brain tissue.

Animals↗
PubMed1993

Effect of aging on EGF stimulated DNA synthesis and EGF receptor levels in primary cultured rat hepatocytes.

Epidermal growth factor (EGF) stimulated DNA synthesis and EGF receptor levels were examined in primary cultured hepatocytes from 6, 12 and 24 month old rats. EGF stimulated DNA synthesis began after 12h and reached a peak at 48 h. Although no age difference was seen in the time course of DNA synthesis, the magnitude of synthesis at the peak time in 12 and 24 month old rat hepatocytes was reduced approximately 50 and 70%, as compared to that at 6 months. Hepatocyte EGF receptors exhibited no age difference in the equilibrium dissociation constant (Kd) or the density (Bmax). These results indicate that EGF stimulated DNA synthesis in rat hepatocytes declines with age, and that this reduction is not due to decreased receptor density or specific binding affinity.

Aging↗
PubMed1993

Changes in G protein-mediated signal transduction in aging and Alzheimer's disease.

Previous reports have shown that there are age-related reductions in muscarinic receptor (mAChR) sensitivity to agonist stimulation. Our research has elucidated the mechanisms involved in this loss. These studies have shown that this decline is the result of decreases in mAChR concentration, reductions in the number of neuronal cells, and altered phosphoinositide (PI)-mediated signal transduction (ST). The decrements in PI-mediated ST are observed as a reduced ability of muscarinic (m) agonists to enhance K(+)-evoked release of DA (K+ ERDA) from striatal slices from old rats. Additional experiments indicated that the locus of the ST deficits appears to be at the mAChR-G protein interface, since attempts to bypass this interface reduced m-enhanced K+ ERDA deficits in the striata from old rats. Moreover, it appears that the ability of mAChR to decouple from their respective G proteins is reduced as a function of age, since carbachol-stimulated low KM GTPase activity was found to be reduced in hippocampal and striatal tissue obtained from old rats. Similar findings were observed in this parameter in AD hippocampus and basal ganglia. Further reductions were seen in carbachol-stimulated low KM GTPase as a function of the duration of the disease. Results are discussed in terms of structural membrane alterations in aging and disease that may lead to reductions in the efficacy of receptor-G protein coupling/uncoupling.

Aging↗
PubMed1993

Effects of age and sex on basal and dopamine-inhibited in vitro prolactin release, and dopamine receptor binding, by the rat adenohypophysis.

We measured basal and dopamine-inhibited pituitary cell prolactin (PRL) release in vitro, and dopamine receptor binding in pituitary homogenates, from intact male and female Wistar rats of varying ages. During 48-72 hours in culture, the baseline secretion rate of PRL from pituitary cells of old (24 months) male rats was less than one-half that from cells of mature (6 months) male rats, whereas the corresponding basal secretion rate of PRL from cells of old female rats was nearly 3-fold greater than that from cells of mature female rats (p < 0.001). After in vitro exposure to various concentrations of dopamine (10(-10)M to 10(-6)M), PRL secretion decreased from pituitary cells of both mature and old rats (p < 0.001). However, repeated measures analysis of variance revealed an age-related dose-dependent decrease in the magnitude of dopamine-inhibited PRL release from cells of both male and female rats (p < 0.001). Dopamine receptor number did not differ with age (3-25 months), but was 2 to 3-fold greater in female than in male rats (p < 0.01). Receptor affinity was decreased with age only in female rats, and was greater in female than in male rats (p < 0.05). These data suggest that the decrease in dopamine-inhibited PRL release from pituitary cells of old male and female rats is not due to altered pituitary dopamine receptor binding, despite certain sex differences.

Age Factors↗
PubMed1993

Decreased striatal D2 dopamine receptor mRNA synthesis during aging.

Decreases in striatal dopamine receptors during aging are related to deficits in motor functions, and are highly correlated with the D2 receptor subtype. Some receptor loss is attributed to cell death, while the remainder is thought to be related to synthetic capacity. We discuss here our findings, for isolated rat striatal nuclei, which indicate a 50% overall decrease in the synthesis of the dopamine D2 mRNA in aged nuclei.

Aging↗
PubMed1993

Pathological characterization of male Wistar rats from the gerontology research center.

Male Wistar rats aged 6-26 months were obtained from the colony of The Gerontology Research Center of the National Institute on Aging, and pathological profiles were assessed. One hundred animals were sacrificed at 6, 12, 18, 21, 24, and 26 months and used for cross-sectional determinations; also, 150 animals were followed longitudinally and sacrificed when clinical signs of moribundity appeared. Renal disease contributed the most common pathology observed in both studies (found in over 70% of the animals examined), with neoplasms a secondary problem (pituitary tumors were by far the most prevalent, with adenomas present in approximately 20% of the animals). This analysis represents the first complete pathological characterization of this commonly used rat model for aging research, and offers an opportunity for comparison with other rat strains.

Aging↗
PubMed1993

Dietary restriction slows age pigment accumulation in the retinal pigment epithelium.

PURPOSE: The accumulation of age pigment, or lipofuscin, in postmitotic cells appears to be a universal feature of the aging process in animals. In mammals, the lipofuscin content of the retinal pigment epithelium (RPE) increases progressively during senescence. Dietary restriction has been shown to slow the rate at which many biologic parameters change during aging. Experiments were conducted to determine if dietary restriction alters the rate of age pigment accumulation in the RPE. METHODS: Male Wistar rats were placed on one of three dietary regimens starting at weaning. One group was fed a nutritionally complete diet ad libitum. Another group was fed the same diet but was only allowed to consume 60% as much food daily as the ad libitum group ate. The final group was fed ad libitum a nutritionally complete diet that had a lower caloric density per gram than the diets fed to the other animals primarily because of the replacement of carbohydrate with oat fiber. Ultrastructural morphometric analysis was used to determine the RPE age pigment content in the first group at 6 months of age, and in all of the groups at 18 months of age. RESULTS: Dietary restriction, achieved either by reducing total food intake or by reducing the caloric content of the diet, resulted in significant decreases in RPE lipofuscin accumulation. CONCLUSIONS: Dietary restriction provides a relatively simple means by which RPE age pigment content can be modulated. This should prove useful in assessing the role of RPE lipofuscin accumulation in age-related retinal disorders. That the oat fiber diet fed ad libitum was almost as effective as restriction of total food intake in slowing RPE age pigment accumulation indicates that the effect of restricted caloric intake is not mediated by almost constant hunger.

Aging↗
PubMed1992

Dietary restriction in nonhuman primates: progress report on the NIA study.

Rhesus and squirrel monkeys have been fed a semisynthetic diet at approximately ad libitum or 30% reduced levels for 3.5 (rhesus group 2) to 4.5 (rhesus group 1 and squirrel) years. Animals have maintained excellent health status as determined by physical examinations, hematology, and blood chemistry. While relative rates of body weight gain in restricted group 1 rhesus and squirrel monkeys have been markedly reduced, DR effects on crown-rump length (body height) have been variable. In addition, numerous physiological and biochemical parameters have been measured, and several exhibit significant cross-sectional age effects. Interestingly, several of these also exhibit possible species and genotype (group 1 and 2 rhesus) differences. A number of physiological parameters are emerging that might be altered by DR; however, further explanation of these effects awaits more extensive and detailed analyses.

Aging↗
PubMed1992

The effects of aging on muscarinic receptor/G-protein coupling in the rat hippocampus and striatum.

In the striatum and hippocampus, there is a loss of sensitivity to muscarinic agonists with age which has been traced to events early in the signal transduction pathway. Our laboratory has therefore focussed on investigations at this level. The current experiments investigate the effects of age on G-protein/receptor interactions by using competitive binding assays to measure the ability of GppNHp to decrease the proportion of receptors bound to G-proteins in the absence and the presence of added Mg2+. L-[3H]Quinuclidinyl benzilate was used as a nonselective ligand and [3H]pirenzepine as an M1 selective ligand. We find that: (1) muscarinic receptors and G-proteins in the striatum appear to become loosely coupled with age, with no change in Mg2+ sensitivity. (2) M1-receptor/G-protein complexes in the hippocampus display increased sensitivity to the presence of Mg2+ with age, with those from old but not young tissue requiring added Mg2+ in order to uncouple. This effect, however, may not be M1 specific.

Aging↗
PubMed1992

Alpha 1-adrenergic stimulation of low Km GTPase in rat striata is diminished with age.

The effect of norepinephrine and epinephrine on the activity of low Km GTPase was studied in striata from young and old rats. Results showed that the amines stimulated the low Km GTPase activity of both young and old animals in a concentration-dependent manner. There was no differential effect of the amines as a function of age, but the stimulated low Km GTPase activity was significantly lower in the aged tissue.

Aging↗
PubMed1992

Alpha 1-adrenoceptors in parotid cells: age does not alter the ratio of alpha 1A and alpha 1B subtypes.

Epinephrine stimulation of 45Ca2+ efflux and inositol 1,4,5-trisphosphate ((1,4,5)IP3) production in parotid cell aggregates from mature rats was greatly inhibited (approximately 70%) by WB 4101 and 5-methylurapidil as compared to a small decrease by chloroethylclonidine (approximately 30%). The combination of WB 4101 or 5-methylurapidil and chloroethylclonidine completely blocked the action of epinephrine. The same relative inhibition was observed with senescent animals. The results suggest (1) that rat parotids contain both alpha 1-adrenoceptor subtypes, i.e., alpha 1A and alpha 1B, in an approximate functional ratio of 70:30, (2) that this relative ratio is not altered during aging, and (3) that both receptors partially mediate 45Ca2+ efflux and (1,4,5)IP3 production in this system.

Adrenergic alpha-Antagonists↗
PubMed1992

Decrement of muscarinic receptor-stimulated low-KM GTPase in striatum and hippocampus from the aged rat.

Previous studies have shown that there is an age-related loss of responsiveness in several different receptor systems (e.g. beta-adrenergic, dopaminergic and muscarinic). Our research, using perifused striatal slices and examining muscarinic agonist enhancement of K(+)-evoked dopamine release, has determined that at least part of the loss of sensitivity in muscarinic receptors (mAChR) may occur early in the post-receptor signal transduction process. The present study was carried out to further characterize and localize this deficit by examining carbachol- and oxotremorine-stimulated low-KM guanosine triphosphatase (GTPase) activity in striatal as well as hippocampal tissue obtained from adult (6 months) and old (24 months) Wistar rats. Receptor stimulated low-KM GTPase catalyzes the conversion of GTP to GDP to end the signal transduction cycle and is an indicator of receptor-G-protein coupling/uncoupling. The results showed that stimulated GTPase activity was significantly reduced in hippocampal and striatal tissue from the old animals. These findings suggest that there may be an age-related coupling/uncoupling deficit between muscarinic receptor and G-proteins, and that this deficit may contribute to the reduced mAChR responsiveness in senescence.

Aging↗