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Biomedical subjects

R J Miller

Publications and source records attributed to R J Miller.

At least 307 records · Page 17Linked to original sources
PubMed1985

Is somatostatin a directly acting cholestatic hormone?

Previous experiments have demonstrated the cholestatic effects of somatostatin administration in several animal species. These effects were confirmed in the rat. Nine pairs of intact awake rats received intravenous sodium taurocholate (23 mg hr-1) to stabilize bile flow, and half were later given somatostatin at doses of 185 micrograms hr-1. After 1 hr of somatostatin the experimental group showed a significant decrease in bile flow compared to the control group. Cholestasis reversed when somatostatin infusion was stopped. An in situ isolated perfused rat liver technique was used to assess the direct effects of somatostatin on biliary flow. In 10 pairs of rat livers, after achieving stable bile flow, half of those perfused (the "experimentals") received continuous (370 micrograms hr-1) somatostatin infusion, while the controls received saline. The percentage change in bile flow from baseline in the somatostatin group was not significantly different from that in controls for any test period. Bile analysis revealed no significant differences between groups for cholesterol, phospholipid, or bile salt concentrations or outputs. These data suggest that somatostatin inhibits bile secretion by some mechanism other than direct inhibition of bile secretory mechanisms.

Animals↗
PubMed1985

Stimulation rate modulates effects of the dihydropyridine CGP 28 392 on cardiac calcium-dependent action potentials.

Calcium (Ca2+)-dependent action potentials were recorded from 22 mM potassium (K+)-depolarized guinea-pig papillary muscle at several different pacing frequencies in the absence and presence of CGP 28 392 (10 microM), a Ca2+ channel agonist. The maximum upstroke velocity (Vmax) of the slow response action potential was measured to determine relative changes in Ca2+ current as a function of pacing frequency. CGP 28 392 increased Vmax more than two fold at low rates of stimulation (1 or 12 pulses min-1), but had no significant effect on Vmax during rapid pulsing (200 pulses min-1). The enhancement of Vmax was dependent upon extracellular [K+]. Increasing extracellular [K+] from 22 mM to 27 mM suppressed the frequency-dependent agonist effects and increased the antagonist effects on Vmax. These results indicate that CGP 28 392 is a partial Ca2+-channel agonist and suggest that its effects on Ca2+ current are voltage-dependent.

Action Potentials↗
PubMed1985

Tolerance and cross-tolerance to the antisecretory effects of enkephalins on the guinea-pig ileal mucosa.

The antisecretory properties of opiates in the guinea-pig ileum have been shown previously to be mediated through interactions with delta-like opiate receptors present in the intestinal mucosa. The present investigation examined the development of tolerance to opioid-induced alterations in intestinal ion transport processes. Osmotic minipumps continuously delivering the prototypic delta-opioid agonist [D-Ala2,D-Leu5]enkephalin (DADLE) (5 micrograms/hr) or the potent mu-opiate agonist fentanyl (10 micrograms/hr) over a 5-day period were implanted s.c. into guinea pigs; control animals did not receive chronic drug infusions. DADLE, DADLE ethylamide and [D-Ala2,D-Met5]enkephalin dose-dependently decreased base-line transepithelial potential difference and short-circuit current in isolated segments of ileal mucosa from untreated control animals, with an order of potency of DADLE greater than [D-Ala2, D-Met5 enkephalin greater than DADLE ethylamide. In tissues from DADLE-infused animals, the antisecretory dose-effect curves of the three enkephalin analogs displayed downward shifts to the right compared to control conditions. In contrast, the potency of DADLE was significantly increased in tissues from animals chronically infused with and rendered physically dependent upon fentanyl. The administration of the opioid antagonists naloxone, diprenorphine or the selective delta-opioid antagonist M 154, 129 produced no significant changes in short-circuit current of mucosal segments from either DADLE- or fentanyl-infused animals. Chronic administration of either DADLE or fentanyl did not significantly alter the effects of nonopioids, bombesin, somatostatin or epinephrine, on ion transport; however, the efficacy but not the potency of neurotensin in increasing short-circuit current was attenuated after chronic DADLE infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Fatigue of accommodation: changes in accommodation after visual work.

The present study was designed to determine whether classical accommodation theory or dual-innervation accommodation theory best explains the visual fatigue effects of prolonged visual work. The accommodation responses of 20 young male adults were measured, using a laser optometer, while they viewed a near target (30 cm), a far target (6 m), or in total darkness. Measurements were made before and after 1-h fatigue sessions, during which subjects either read monocularly presented slides of text at near or far distances, or remained in darkness. There were no significant changes in near or far target static accommodation as a result of any of the fatigue sessions. Dark focus accommodation shifted inward after the near target viewing task and after prolonged dark viewing. The results are discussed in terms of their implications for research in accommodative fatigue, and their relation to other current research.

Accommodation, Ocular↗
PubMed1984

Depolarization-induced increases in intracellular free calcium detected in single cultured neuronal cells.

Microspectrofluorometry was used to examine intracellular free calcium changes in single NG108-15 neurons loaded with the Ca2+ sensitive probe, quin2. The changes in intracellular free Ca2+ were induced either by depolarizing cells with high K+ or veratridine or by the addition of ionomycin. Ca2+-free medium and various inorganic and organic calcium-channel blocking agents blocked changes in intracellular free Ca2+ levels, indicating that Ca2+ entry is most likely through voltage-sensitive calcium channels.

Calcium↗
PubMed1984

Enkephalin-like immunoreactivity in rat area postrema: ultrastructural localization and coexistence with serotonin.

The ultrastructure of enkephalin-containing neurons and their capacity to take-up [3H]serotonin were examined in the area postrema. Untreated adult rats and rats with intraventricular infusions of 10(-4) M tritiated serotonin, 5-hydroxytryptamine [( 3H]5-HT) were perfused with 4% paraformaldehyde and 0.2-0.5% glutaraldehyde. Coronal Vibratome sections through the area postrema from both groups of animals were immunocytochemically labeled with an antiserum to leucine Leu5-enkephalin. The sections from the animals infused with the isotope subsequently were processed for autoradiography. Enkephalin-like immunoreactivity (ELI) was detected in perikarya, dendrites, axons and axon terminals most frequently located along the ventricular and ventrolateral portions of the area postrema. The labeled perikarya were few in number and were characterized by a thin rim of cytoplasm containing peroxidase immunoreactivity. Dendrites and terminals containing ELI formed synapses primarily with unlabeled axon terminals and dendrites, respectively. However, terminals containing ELI also formed synaptic junctions with other unlabeled axon terminals. Appositions between enkephalin-containing processes and modified glia were occasionally seen near the ventricular surface. In sections processed for both immunocytochemistry and autoradiography, approximately 5% of the terminals containing ELI showed uptake of [3H]5-HT. We conclude that neurons containing ELI are primarily, but not exclusively, associated with other intrinsic neurons or afferents in the rat area postrema and that some of the enkephalin-labeled terminals have the capacity to take-up serotonin. Specificity of uptake of [3H]5-HT in neurons containing endogenous serotonin and factors which may contribute to the low probability of detecting both peroxidase and autoradiographic markers in single sections are discussed.

Animals↗
PubMed1984

The effects of dihydropyridines on neurotransmitter release from cultured neuronal cells.

Depolarizing stimuli increase the release of transmitter substances from cultured PC12 pheochromocytoma cells and reaggregate cultures of mouse mesencephalic dopamine neurones. We measured the stimulated release of (3H) norepinephrine and (3H) dopamine from these systems respectively. In the cultured mouse dopaminergic neurones, several organic calcium channel blockers including nitrendipine, D-600, verapamil and diltiazem were unable to inhibit potassium-evoked transmitter release. However, release was blocked by 3 mM cobalt. The novel dihydropyridine calcium channel agonist BAY K8644 also had no effect on basal or evoked dopamine release. In contrast, BAY K8644 greatly stimulated the potassium-evoked release of (3H) norepinephrine from PC12 cells. The BAY K8644 enhanced release could be blocked by the dihydropyridine antagonist nitrendipine. These results indicate that while stimulus-secretion coupling in the PC12 cell line involves dihydropyridine sensitive calcium channels, this is not the case in primary cultured neurones.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1984

Substance P, neurotensin, enkephalin, and catecholamine-synthesizing enzymes: light microscopic localizations compared with autoradiographic label in solitary efferents to the rat parabrachial region.

The immunocytochemical localizations of substance P, neurotensin, enkephalin and the catecholamine-synthesizing enzymes tyrosine hydroxylase and dopamine-beta-hydroxylase were examined in the rat parabrachial region. The immunoreactivity for each marker was compared with the distribution of superimposed autoradiographic labeling of parabrachial afferents after unilateral injection of 3H-amino acids into the caudal portion of the medial nucleus of the solitary tract (m-NTS). Substance-P- and neurotensinlike immunoreactivity (SPLI and NTLI, respectively) were localized primarily in varicose processes in the ventrolateral quadrant of the parabrachial region. The SPLI and NTLI were differentially localized with respect to each other; however, both peptides were detected in regions of the parabrachial containing dense autoradiographic label. In contrast, enkephalinlike immunoreactivity (ELI), tyrosine hydroxylase, and dopamine-beta-hydroxylase were detected in processes and a few perikarya located outside the ventrolateral parabrachial region. The ELI was primarily in the dorsolateral, and the catecholamine-synthesizing enzymes were primarily in the medial parabrachial regions which contained sparse autoradiographic labeling of transported amino acids. We conclude that in the rat parabrachial region, SPLI and NTLI are contained within two distinct populations of afferents which may originate from perikarya in the caudal m-NTS, whereas ELI and the catecholamines are more likely to be found in other afferents or possibly in intrinsic neurons.

Animals↗
PubMed1984

Evidence for a role of phospholipase activity in the serum stimulation of Na+ influx in human fibroblasts.

Serum stimulation of cultured human fibroblasts activates a Na+ influx via an amiloride-sensitive Na+/H+ exchange system. Evidence is presented which indicates that phospholipase activity is an important component of the mechanism by which mitogen receptor occupation leads to activation of Na+/H+ exchange. Serum stimulation of Na+ flux is effectively blocked by inhibitors of phospholipase activity such as mepacrine and U-1002. The Ki values for inhibition of Na+ flux by these agents (10 microM and 18 microM, respectively) are comparable to their Ki values for inhibition of serum-stimulated arachidonic acid release. In contrast, the activation of Na+ influx produced by the divalent cation A23187 is not affected by phospholipase inhibitors indicating that these agents specifically block mitogen activation of Na+ flux rather than nonspecifically disrupting the membrane's ability to perform Na+/H+ exchange. The phospholipase activator melittin stimulates Na+ influx in the absence of mitogens at concentrations that cause a comparable stimulation of arachidonic acid release. The melittin-stimulated Na+ influx is inhibited by amiloride and mepacrine, suggesting that melittin activation of phospholipase activity leads to the activation of the Na+/H+ exchange system. In addition, chronic treatment of cells with dexamethasone, which is known to induce an endogenous phospholipase inhibitor in human fibroblasts, leads to a substantial inhibition of the serum stimulation of both Na+ influx and arachidonic acid release. When taken together, these data support the involvement of phospholipase activity in the serum stimulation of the Na+/H+ exchange system.

Amiloride↗
PubMed1984

Evidence that the medial and dorsal raphe nuclei mediate serotonergically-induced increases in prolactin release from the pituitary.

Electrolytic lesions of the medial (MR) or dorsal (DR) raphe nucleus significantly antagonized serum prolactin elevations produced by 5-hydroxytryptophan (5-HTP) in rats pretreated with fluoxetine or citalopram, (serotonin (5-HT) uptake blockers). Lesioned animals in which total blockade of serum prolactin elevations was observed also had total blockade of 5-HT accumulation in the median eminence. However, the increase in serum prolactin levels produced by 5-HTP plus 5-HT reuptake blockade in lesioned rats was not significantly different from sham-operated rats if as little as 15-20% of control median eminence accumulation was present. Serum prolactin elevations produced by quipazine, a direct acting 5-HT agonist, were not significantly affected by MR lesions. On the basis of these results, we suggest that: (1) serum prolactin elevations following 5-HT reuptake blockade plus 5-HTP are correlated with 5-HT concentration in the median eminence; (2) lesion-induced antagonism of 5-HTP-induced prolactin elevation is critically dependent upon complete blockade of median eminence 5-HT accumulation; and (3) 5-HT neurons arising from cell bodies located in the MR and DR are necessary for endogenous serotonergically mediated effects on prolactin secretion in the rat.

Animals↗
PubMed1984

Effects of crepuscular photoenvironment on light-induced behavior of Daphnia.

Phototactic response rates in the aquatic crustacean Daphnia magna were found to increase greatly when cultured under a lighting regime that included simulation of sunset and sunrise. The changes in intensity and color of the crepuscular periods are known to be the primary stimulus for vertical migrations of many planktonic forms, and may have importance to many other animals as well. The value of this type of lighting to investigators of animal behavior and physiology is discussed.

Animals↗
PubMed1984

Ultrastructural relation between cortical efferents and terminals containing enkephalin-like immunoreactivity in rat neostriatum.

The interrelationships between cortical efferents and terminals containing enkephalin-like immunoreactivity (ELI) were examined by combining anterograde degeneration with electron microscopic immunocytochemistry in the adult rat neostriatum. Two days following unilateral removal of the cerebral cortex, the brains were fixed by aortic arch perfusion, then sectioned and processed for the immunocytochemical localization of an antiserum directed against methionine (Met5)-enkephalin. The observed relationships between the degenerating cortical efferents and immunocytochemically labeled terminals were of two types. In the first, the degenerating and ELI containing terminals converged on the same unlabeled dendrite or dendritic spine. In the second, terminal and preterminal axons of the ELI containing neurons had one surface directly apposed to the plasma membrane of a degenerating axon terminal. These findings support the concept that neurons containing opioid peptides and cortical efferents modulate the output of common recipient neurons and may also directly interact with each other through presynaptic axonal mechanisms in the rat neostriatum.

Animals↗
PubMed1984

Interactions of maitotoxin with voltage-sensitive calcium channels in cultured neuronal cells.

The dinoflagellate toxin maitotoxin (MTX) stimulated 45Ca2+ uptake in cultured NG108-15 neuroblastoma X glioma cells. Depolarizing stimuli (e.g., 50 mM K+) produced an immediate stimulation in Ca2+ uptake, whereas that produced by MTX occurred only after a lag period of about 2 min. MTX did not stimulate Ca2+ uptake into fibroblasts. Both 50 mM K+- and MTX-stimulated Ca2+ uptake was blocked by organic calcium channel antagonists (nitrendipine, D-600, diltiazem) at very low concentrations. Cd2+ was also a potent blocker. The novel dihydropyridine BAY K8644 enhanced Ca2+ uptake in the presence of 50 mM K+ but had no effect in 5 mM Ca2+. However, in the presence of MTX, BAY K8644 stimulated Ca2+ uptake in 5 mM K+. The effects of MTX were not blocked by tetrodotoxin but were decreased in Na+-free medium. MTX did not stimulate Na+ uptake into NG108-15 cells and did not alter [3H]nitrendipine binding to rat brain cortical synaptosomes. It is concluded that MTX may alter the voltage dependence of calcium-channel activation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗