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M L Roberts

Publications and source records attributed to M L Roberts.

At least 55 records · Page 3Linked to original sources
PubMed1988

Context-US learning in Aplysia californica.

Two experiments explored learning about the relation between an unconditioned stimulus (US) and the context in which that US was delivered in Aplysia californica. Subjects were exposed to 2 different contexts. They received a series of moderate electric shock USs in one context but not in the other. Experiment 1 revealed that the context-shock pairings were sufficient to establish an association between that context and the shock. That association was demonstrated by the ability of the reinforced context to enhance a defensive reflex and to reduce learning about a conditioned stimulus (CS) that was subsequently paired with the shock US. Experiment 2 provided evidence that the context-US association could be extinguished by simple nonreinforced exposure to the reinforced context. These results show that context conditioning is not unique to vertebrate learning. We argue that this learning is difficult to accommodate within current contiguity-based neuronal models of learning.

Animals↗
PubMed1988

Conditional discrimination learning in Aplysia californica.

Two experiments examined whether the relation between a conditioned stimulus (CS) and an unconditioned stimulus (US) might be brought under the control of contextual stimuli in the invertebrate Aplysia californica. Subjects received exposure to 2 different contexts. In both experiments, a tactile CS was paired with a shock US in one of those contexts. In the other context, that tactile CS was either nonreinforced (Experiment 1) or explicitly unpaired with the shock US (Experiment 2). Responding to the CS during a subsequent test was greater in the context in which that CS had been paired with the US compared with the context in which it had been nonreinforced or unpaired. These findings are discussed in terms of theories of conditional discrimination learning.

Animals↗
PubMed1986

(Na+ +K+)-ATPase activity in kidney basolateral membranes of non insulin dependent diabetic rats.

Insulin resistant, Type II diabetes mellitus (NIDD) in a rat animal model results in profound changes in basal and insulin-stimulated membrane (Ca2+ +Mg2+)-ATPase activity in kidney basolateral membrane (BLM) preparations. We find that NIDD in these animals does not result in similar changes in membrane (Na+ +K+)-ATPase activity. Basal enzyme activity was the same in diabetic and control animals. Insulin treatment of diabetic animals in vivo resulted in hyperinsulinemia and increased BLM (Na+ +K+)-ATPase, while food restriction for 18 hr resulted in lowered enzyme activity. There was no direct effect of insulin on (Na+ +K+)-ATPase activity in isolated membranes from any of the animal groups. Thus, physiologic perturbations which alter insulin sensitivity and glucose homeostasis are accompanied by altered levels of (Na+ +K+)-ATPase activity. Lower levels of this membrane enzyme activity appear to be associated with optimal insulin action.

Animals↗
PubMed1985

Receptor interactions in stimulation of hydrolysis of inositol phospholipids.

The amount of carbachol-induced hydrolysis of inositol phospholipid in the mouse exocrine pancreas is reduced when cholecystokinin octapeptide, an agonist which works through a separate class of receptors, is also present. This effect does not appear to be due to depletion of inositol phospholipid from the cell membranes. These results indicate that the hydrolysis of inositol phospholipid is not always dependent on the number of receptors occupied and that the different classes of receptors share at least one component in the response system.

Animals↗
PubMed1985

The effects of gamma-hexachlorocyclohexane on amylase secretion and inositol phospholipid metabolism in mouse pancreatic acini.

Dispersed mouse and guinea-pig pancreatic acini were used to examine the effects of the inositol analogue, gamma-hexachlorocyclohexane (lindane) on agonist-stimulated amylase secretion. Secretion from mouse acini in response to carbachol and cholecystokinin octapeptide (CCK-8) was reduced by lindane. Similarly, amylase release from guinea-pig acini stimulated by carbachol was abolished by lindane. These acini, however, still remained responsive to dibutyryl-cAMP with only a slightly diminished secretion to this agent. Inositol phospholipid synthesis and hydrolysis was stimulated in mouse acini by both carbachol and CCK-8. Although hydrolysis of these lipids in response to CCK-8 was reduced by only 18%, stimulation of inositol phospholipid synthesis by either agonist was abolished by lindane. Dose-response curves for inositol phospholipid synthesis stimulated by carbachol and CCK-8 in mouse acini were biphasic and superimposable with those of amylase secretion. In contrast, the dose-response curve for phosphoinositide hydrolysis was sigmoid and clearly separable from that of synthesis. Reducing the external Ca2+ concentration caused the dose-response curves for carbachol- and CCK-8-induced inositol phospholipid synthesis to be displaced to the right, as has been observed for amylase secretion. A23187 was also found to induce amylase secretion and inositol phospholipid synthesis, and both of these responses were inhibited by lindane. Amylase secretion and inositol phospholipid synthesis may, therefore, be closely related events in the exocrine pancreas. Lindane may provide a valuable tool with which to determine the role of inositol phospholipid metabolism in stimulus-response coupling.

Amylases↗
PubMed1984

The contribution of inositol exchange to agonist-stimulated breakdown of myo- [2-3H] inositol-labelled phosphatidylinositol in mouse exocrine pancreas.

Agonists stimulate the release of myo-inositol from phosphatidylinositol (PtdIns) labelled in vivo with myo-[2-3H] inositol. In the presence of lithium, which inhibits myo-inositol-1-phosphatase, the compound which accumulates following the breakdown of pre-labelled PtdIns is inositol-1-phosphate. This indicates that the agonist-stimulated release of the head group from this lipid is not the result of inositol exchange and is due to phosphodiesterase activity. The total amount of 3H-labelled compounds released from PtdIns in the presence and absence of lithium is the same, which indicates the labelled compounds which are released are not re-incorporated. Agonist-induced release of myo-[2-3H] inositol can be used as a reliable indication of PtdIns breakdown in the exocrine pancreas.

Animals↗
PubMed1984

Schistosoma mansoni egg granuloma size reduction in challenged baboons after vaccination with irradiated cryopreserved schistosomula.

Young male baboons born in captivity were immunized with an attenuated, cryopreserved schistosomular vaccine derived from gamma-irradiated (50 krad) cercariae of the Puerto Rican strain of Schistosoma mansoni. Protection against a heterologous Kenyan strain of S. mansoni, after percutaneous infection, was assessed. Partial protection (33-53% reduction in worm burden) was obtained in three of six vaccinated-challenged baboons, an unremarkable result. Of greater interest was the fact that all six unvaccinated-challenged control baboons, but only one of the six vaccinated-challenged baboons, had macroscopic egg granulomas on their liver surfaces. This difference in granuloma size was substantiated by measuring hepatic and colonic granulomas. The mean (+/- SEM) hepatic and colonic granuloma diameters for the six unvaccinated baboons were 406 +/- 38 micron and 313 +/- 27 micron, respectively, and for the five "typical" vaccinated-challenged baboons the mean diameters were 283 +/- 27 micron and 202 +/- 23 micron, respectively. Both hepatic and colonic granulomas were significantly smaller in the five typical vaccinated-challenged baboons. Not only did the exceptional vaccinated-challenged baboon have very large hepatic and colonic granulomas, but also it was the only one of its group whose mesenteric lymph node cells were not suppressed in their in vitro proliferative response to a schistosome antigen. These results strongly suggest that granuloma size reduction in the majority of the vaccinated baboons was the result of immunoregulation--i.e., the small postvaccination granulomas were "modulated." Despite their small size, hepatic granulomas in the typical vaccinated baboons were apparently as effective in sequestering egg toxins and preventing hepatocyte damage as the larger granulomas of the control baboons. Smaller, less obstructive granulomas are thought to be more beneficial to the host than large, vigorous granulomas, with respect to lessening chronic disease. The present results give encouragement that a vaccine to ameliorate disease in human schistosomiasis is possible. This effect should add to the attractiveness of partial protection against challenge infections conferred by attenuated larval vaccines, as reported by others, to yield a dually beneficial vaccine for human use.

Animals↗
PubMed1983

The involvement of protein phosphorylation in stimulus-secretion coupling in the mouse exocrine pancreas.

Secretagogue-induced protein phosphorylation was studied in the mouse pancreas in vitro, by using polyacrylamide-gel electrophoresis to separate the labelled proteins. Muscarinic cholinergic agonists increased the phosphorylation of a single band, which corresponded to Mr 32000, when the tissue was incubated with Ca2+ present in the extracellular medium, but not in Ca2+-free Krebs solution. In the presence of Ca2+, ionophore A23187 stimulated phosphorylation of the same band. The dose-response curve for carbachol-induced phosphorylation was biphasic, with maximum response at 1.0 microM-carbachol, and lesser responses when greater concentrations were used. This resembles the dose-response curve for carbachol-induced amylase secretion. The data suggest that the muscarinic-agonist-induced protein phosphorylation is stimulated secondarily to elevation of cytosol [Ca2+] and do not support the idea that diacylglycerol formed from hydrolysis of phosphatidylinositol is the activator of the protein kinase. Derivatives of cyclic AMP stimulated phosphorylation of bands corresponding to Mr 95500, 32000 and 20000. The effects of dibutyryl cyclic AMP and bethanechol on the protein of Mr 32000 were not additive, suggesting that the two agents produced phosphorylation of the same site(s) on this protein. Since derivatives of cyclic AMP, which are not very effective secretagogues in the exocrine pancreas, stimulate phosphorylation of the protein of Mr 32000, it is difficult to argue that phosphorylation of this particular protein leads to protein secretion.

Animals↗
PubMed1982

Calcium-dependent K+ efflux from rat submandibular gland. The effects of trifluoperazine and quinidine.

The Ca2+-dependent K+ efflux from rat submandibular gland was studied using a K+-sensitive electrode. A K+ efflux was induced by either adrenalin or by using the divalent cation ionophore A23187 plus added Ca2+ to bypass the receptor mechanism. Trifluoperazine, which was used to investigate the role of calmodulin, was found to block the adrenalin-induced K+ efflux but not the A23187/Ca2+-induced K+ efflux. The adrenalin-induced K+ efflux was abolished by quinidine and the A23187/Ca2+-induced K+ efflux was significantly reduced by quinidine. In other experiments, the presence of indomethacin did not inhibit the adrenalin-induced K+ efflux, and exogenously added arachidonic acid did not induce a K+ efflux. It is concluded that neither prostaglandin synthesis, nor a cytosolic Ca2+-calmodulin complex is involved in the agonist-induced K+ efflux from rat submandibular gland. A similarity between the Ca2+-dependent K+ efflux mechanism of erythrocyte ghosts and submandibular tissue is indicated by their common response to quinidine.

Animals↗
PubMed1982

The role of calcium in agonist-stimulated hydrolysis of phosphatidylinositol in mouse pancreas.

The effects of Ca2+ on agonist-stimulated hydrolysis of myo-[2-3H]inositol-labelled phosphatidylinositol in mouse pancreas in vitro, were studied. The increase in cytosol Ca2+ concentration produced by the ionophore A23187 did not stimulate the breakdown of phosphatidylinositol. Cholecystokinin-octapeptide (CCK-8) stimulated the hydrolysis of phosphatidylinositol under conditions in which intracellular calcium stores were depleted. The breakdown of phosphatidylinositol was stimulated by bethanechol and CCK-8 in Ca2+ -free Krebs solution, and the addition of Ca2+ to the medium potentiated the effects of these agonists. Lanthanum significantly reduced bethanechol and CCK-8-stimulated hydrolysis of phosphatidylinositol in Krebs solution, but was without effect in Ca2+ -free Krebs solution. The results of this study support the proposal that hydrolysis does not occur as a result of Ca2+ mobilization and may be involved in Ca2+ gating in the pancreas.

Animals↗
PubMed1982

Calcium causes the biphasic dose-response curve for pancreatic amylase secretion.

High concentrations of bethanechol (10(-4) to 10(-3) M) were effective stimulants of amylase secretion from the mouse pancreas if incubations are performed in low [Ca2+] (0.1 mM) solutions but not if normal Krebs solution (2.56 mM Ca2+) was used. This inhibitory effect of Ca2+ at high secretagogue concentrations did not appear to be mediated through the microtubules or microfilaments.

Amylases↗
PubMed1981

Mepacrine inhibition of bradykinin-induced contractions of the rabbit ear vein.

Bradykinin induced concentration-dependent contractions in spiral strip preparations of the central vein of rabbit's ears. These contractions require the presence of Ca2+ in the extracellular medium. Mepacrine (2.1 to 42.3 mumol/l) significantly reduced these contractions. Since indomethacin (28 mumol/l) did not reduce the contractions produced by bradykinin, the effect of mepacrine is not explained by inhibition of prostaglandin synthesis. Procaine (10(-7) to 10(-4) mol/l) did not reduce the contractions produced by bradykinin and thus is does not seem that mepacrine acts through a non-specific, local anaesthetic effect. Mepacrine reduced the phosphatidate-mediated transfer of 45Ca from an aqueous phase to an organic phase. It has recently been proposed that phosphatidate may be the Ca2+ ionophore in smooth muscle. However, in the present experiments procaine was about as potent as mepacrine in inhibiting phosphatidate-mediated 45Ca transfer, and since it did not reduce the contractile responses these results do not support the concept that mepacrine inhibits contractions by reducing the Ca2+ influx via a phosphatidate ionophore.

Animals↗
PubMed1981

Agonist-stimulated breakdown of myo-[2-3H] inositol-labelled phosphatidylinositol in mouse pancreas.

Agonist-stimulated hydrolysis of phosphatidylinositol (PI) in cell membranes has been proposed to lead to an increase of cytosol calcium concentration and activation of the cellular response in certain smooth muscles and glands. A method is described which allows the rapid, reproducible measurement of hydrolysis of phosphatidylinositol in mouse pancreas. The technique involves the in vivo labelling of the pancreas with myo-[2-3H] inositol. The majority of the label incorporated into phospholipids is in the form of PI, with only a small proportion of label in di- and tri-phosphoinositides. Tissue pieces of the labelled pancreata are incubated in vitro in the presence or absence of secretagogues, and the PI in homogenates of these pieces is precipitated with trichloroacetic acid. No PI remains in the acid-soluble supernatant. This technique does not require the time-consuming extraction and chromatographic separation of lipids which has been necessary in other assays of PI hydrolysis. Using this method, we have confirmed that PI breakdown is stimulated by carbachol and cholecystokininoctapeptide in the presence or absence of extracellular Ca2+. Agonist-stimulated hydrolysis of PI was potentiated by extracellular Ca2+, and was not dependent on agonist-activated Na+ influx. This technique will facilitate the investigation of the importance of PI breakdown in stimulus-response coupling.

Animals↗
PubMed1980

A comparison of the actions of acetylcholine and bradykinin on the guinea pig ileum.

Procaine (8.5 x 10(-5) M) inhibited the action of acetylcholine but not that of bradykinin on the guinea pig ileum. Attempts were made to identify the difference in stimulus-response coupling which would explain this difference in sensitivity. The responses to both agonists were dependent upon the presence of Ca2+ in the extracellular fluid, were inhibited to approximately the same extent by the addition of 0.25 mM Mn2+ to the bathing fluid and were equally sensitivity to reduction in Na+ concentration of the extracellular fluid. Neither acetylcholine nor bradykinin could provoke ileal contraction when Sr2+ was substituted for Ca2+. Thus there was no indication of the difference in the stimulus-response pathways for the two agonists which must exist to explain the differential sensitivity to procaine.

Acetylcholine↗