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Biomedical subjects

R J Miller

Publications and source records attributed to R J Miller.

At least 289 records · Page 16Linked to original sources
PubMed1986

Instrument myopia conceptions, misconceptions, and influencing factors.

The literature on instrument myopia is reviewed, with the review organized around three principal objectives. One is to describe and discuss various factors that may influence the degree to which instrument myopia is manifested, including monocular vs. binocular viewing, age, direction of focus, illumination level, fatigue, magnification, astigmatic variations, optical decentration, perceived proximity of the target and peripheral surround, and experience. The second objective is to discuss the intermediate resting state conception of accommodation, its application to instrument myopia, and its strengths and weaknesses as applied to the available literature. The third objective is to summarize the salient problems in the instrument myopia literature, and to present a set of recommendations for guiding future work.

Accommodation, Ocular↗
PubMed1986

Protein kinase C mediated regulation of calcium channels in PC-12 pheochromocytoma cells.

Depolarization of PC-12 pheochromocytoma cells with K+ produces an immediate increase in catecholamine release. The stimulation of release is blocked by Co2+, removal of extracellular Ca2+ or by dihydropyridine drugs such as nitrendipine. Release is enhanced by other dihydropyridines such as BAY K8644. Release is accompanied by a voltage dependent uptake of 45Ca2+ which is also blocked by Co2+ or nitrendipine and enhanced by BAY K8644. The phorbol ester phorbol 12-myristate-13-acetate (TPA) in the range 10(-9)-10(-6) M produced little effect by itself but augmented the K+ evoked release of catecholamine. An analog of TPA which does not activate protein kinase C was ineffective. In contrast, TPA in the same concentration range blocked influx of 45Ca2+ induced by 70 mM K+ or 70 mM K+/BAY K8644. 45Ca2+ influx produced by A23187 was not blocked by TPA. The results suggest a system by which protein kinase C may regulate the output of transmitters from secretory cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Simplified non-enzymatic technique for isolation of epithelium and muscle from the dog prostate gland.

Epithelium and muscle from the normal dog prostate were isolated with a rapid, simple, non-surgical separation (NSS) technique, involving mechanical agitation of organ cubes in a high concentration (30 microM) of EDTA for tissue dispersion, and gentle pressure filtration for recovery of epithelium and muscle. Derivation of this NSS procedure utilized the guinea pig seminal vesicle, since it can be surgically separated (SS) into pure epithelium and muscle to serve as controls for the biochemical viability of NSS prepared tissues. The NSS procedure adopted for use yielded not only pure (greater than 95%) epithelium and muscle from intact seminal vesicle, but also activities of 5 alpha-reductase and concentrations of the cytosol estrophile in each tissue, which were not significantly different from the SS counterparts. In the dog prostate gland, the concentrations of 5 alpha-reductase and the cytosol estrophile in the NSS epithelium were 1.58 and 0.43 of the NSS muscle, respectively.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1986

Glucagon lowers canine biliary cholesterol output at physiologic doses.

Pharmacologic doses of glucagon affect canine bile secretion by increasing bile flow while simultaneously decreasing biliary cholesterol output. The present study was performed to determine if physiologic doses of glucagon reduce biliary cholesterol output. Awake dogs received both intravenous 1% sodium taurocholate (50 ml/hr) to stabilize bile flow and somatostatin (12 micrograms/kg/hr) to suppress endogenous pancreatic hormone release. Suppression was documented by significant decreases in portal plasma glucagon and insulin levels. During experimental trials, dogs received, in addition, glucagon (5 ng/kg/min) infused via a splenic vein catheter. Bile flow significantly decreased during the initial hour of somatostatin infusion but increased significantly only in experimental trials during subsequent glucagon infusion. Biliary cholesterol output showed no change during control studies (N = 9), but decreased significantly during glucagon infusion studies (N = 11). Biliary phospholipids and bile salts failed to show any changes during glucagon infusion. These data demonstrate that glucagon at physiologic levels influences both the volume and cholesterol content of bile and suggest the mechanism of decreasing cholesterol output must be independent of pathways for influencing bile salt or phospholipid secretion.

Animals↗
PubMed1986

Multiple calcium channels mediate neurotransmitter release from peripheral neurons.

We examined the effects of dihydropyridine drugs on evoked neurotransmitter release from cultured neonatal rat sensory and sympathetic neurons. Depolarization with K+-rich solutions increased the release of substance P from cultured sensory neurons. This release was enhanced by BAY K8644 and (+)-202791 and was blocked by a variety of other dihydropyridines including (-)-202791, by Co2+, or in Ca2+-free solutions. K+-rich solutions also stimulated the release of [3H]norepinephrine from cultured sympathetic neurons. This release was also completely blocked by Co2+ or in Ca2+-free solution. In contrast to the situation in sensory neurons, however, the evoked release of [3H]norepinephrine was completely resistant to the blocking effects of dihydropyridine such as nimodipine. However, BAY K8644 was able to enhance the evoked release of [3H]norepinephrine, and this enhancement was blocked by nimodipine. These results are discussed in relation to the possible participation of multiple types of calcium channels in the release of neurotransmitters.

Animals↗
PubMed1986

Brain voltage-sensitive calcium channel subtypes differentiated by omega-conotoxin fraction GVIA.

We have studied the voltage-activated influx of Ca2+ into synaptosomes. Rapid 45Ca2+ influx into synaptosomes, measured at 1 sec, was blocked by predepolarization and by low concentrations of cadmium (IC50, 1 microM), as anticipated for voltage-sensitive calcium channels (VSCCs). However, fluxes were insensitive to dihydropyridine drugs that block or activate VSCCs, including nitrendipine, Bay K 8644, and (+)- and (-)-PN202-791. Phenylalkylamine calcium antagonists, including verapamil and desmethoxyverapamil, blocked 45Ca2+ uptake in a nonspecific fashion. The peptide omega-conotoxin fraction GVIA (omega-CgTx GVIA) blocked 45Ca2+ uptake in a biphasic fashion, with a 30% reduction at 50 pM toxin and a further decrease at concentrations greater than 5 nM. The toxin inhibited neurotransmitter release from synaptosomes in nanomolar concentrations, corresponding to its low-affinity effects on 45Ca2+ influx. omega-CgTx GVIA also inhibited depolarization-induced increases in intracellular Ca2+ concentration in single hippocampal and striatal neurons. These findings indicate that omega-CgTx GVIA blocks VSCCs in both cell bodies and nerve terminals and that the predominant form of VSCC in nerve terminals is the dihydropyridine-insensitive N type.

Animals↗
PubMed1986

Nerve growth factor modulates the drug sensitivity of neurotransmitter release from PC-12 cells.

The release of catecholamines from adrenal chromaffin cells is known to be blocked by dihydropyridines, such as nitrendipine, and enhanced by others, such as BAY K8644. On the other hand, release from sympathetic neurons is predominantly insensitive to these agents. Release of [3H]norepinephrine from undifferentiated PC-12 pheochromocytoma cells resembles that from chromaffin cells in that it is extremely sensitive to dihydropyridines. Following differentiation, however, release of catecholamine becomes predominantly insensitive to both nitrendipine and BAY K8644. Under both growth conditions, release remains completely blocked by 3 mM Co2+ or by removal of Ca2+ from the release media. Dose-response curves to K+ show that following differentiation, cells become more sensitive, releasing transmitter at lower K+ concentrations. In contrast, depolarization-induced uptake of 45Ca2+ remains sensitive to dihydropyridines and shows similar sensitivity to K+ stimulation in both growth conditions. These results can be explained by invoking a model involving dihydropyridine-sensitive and -insensitive types of voltage-sensitive calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Maitotoxin-induced release of gamma-[3H]aminobutyric acid from cultures of striatal neurons.

The potent marine toxin, maitotoxin, induced the release of gamma-[3H]aminobutyric acid (GABA) from reaggregate cultures of striatal neurons in a dose-dependent manner. Maitotoxin-induced release occurred following a lag period of several minutes and was persistent. Release induced by 70 mM K+ on the other hand was immediate and transient in nature. Co2+ (3 mM) and Cd2+ (1 mM) inhibited maitotoxin-induced release of GABA as did removal of extracellular Ca2+. However, the organic calcium antagonists nisoldipine, nitrendipine, and D-600 at concentrations of 10(-6) M did not block maitotoxin-induced or 70 mM K+-induced release. High concentrations of D-600 (10(-4) M) partially blocked both maitotoxin- and 70 mM K+-induced release. The dihydropyridine calcium agonist BAY K8644 (10(-6) M) did not enhance maitotoxin-induced or 70 mM K+-induced release. Replacement of Na+ in the incubation medium with choline led to an increased basal output of GABA and an apparent inhibition of the effect of maitotoxin. These data are discussed with reference to the hypothesis that maitotoxin can directly activate voltage-sensitive calcium channels.

Animals↗
PubMed1986

Neuropeptide Y: a powerful modulator of epithelial ion transport.

Neuropeptide Y (NPY) is a major gut peptide localized in the intestinal mucosa of several mammalian species. Ileal mucosa from rabbit and guinea-pig was mounted in Ussing chambers in order to study the effect of NPY on short circuit current. Neuropeptide Y inhibited the short circuit current when applied to the serosal side of the tissue. The maximum change in short circuit current was -50 +/- 6 microA cm-2 in the rabbit ileum and -49 +/- 14 microA cm-2 in the guinea-pig ileum. The EC50 was 3 X 10(-8) M in both species. Pretreatment of rabbit ileum with the alpha 2-adrenoceptor antagonist, yohimbine (1 X 10(-6) M) for 10 min did not reduce the response of the tissue to neuropeptide Y (1 X 10(-7) M). When applied serosally to rabbit ileal mucosa, the related peptide YY caused a maximum change in short circuit current of -60 +/- 13 microA cm-2; the EC50 was 2 X 10(-9) M. Isotopic flux studies in rabbit ileum showed that 1 X 10(-7) M neuropeptide Y enhanced mucosal-to-serosal Na+ and Cl- fluxes and reduced serosal-to-mucosal Cl- flux. Replacement of chloride with gluconate on both sides of the tissue significantly reduced the change in short circuit current produced by neuropeptide Y (1 X 10(-7) M), as did a similar replacement of bicarbonate. It is concluded that neuropeptide Y and peptide YY are the most potent neurotransmitters or hormones so far described in their ability to attenuate electrogenic transport in the small intestine.

Animals↗
PubMed1986

Widespread distribution of dihydropyridine-sensitive calcium channels in the central nervous system.

We have used microspectrofluorimetry and the Ca2+-sensitive dye fura-2 to analyze the effects of dihydropyridine drugs on the voltage-sensitive influx of Ca2+ into central nervous system neurons grown in primary culture. Depolarization, induced by raising [K+]o, produced a rapid increase in [Ca2+]i measured in single neurons from the cortex, hippocampus, striatum, septum, and cerebellum. These increases were slightly attenuated when external Na+ was replaced by choline+ and were absent in Ca2+-free (1 mM EGTA) media. The depolarization-induced uptake of Ca2+ by neurons from all regions of the brain was enhanced by the dihydropyridine agonist BAY K8644 (1 microM). The dihydropryidine antagonist nitrendipine (1 microM) inhibited calcium influx into hippocampal and striatal neurons by 79% and 31%, respectively, indicating that different routes of voltage-dependent calcium influx predominate in neurons from different brain regions. The results establish the widespread distribution of functional dihydropyridine-sensitive Ca2+ channels in the central nervous system.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Calcium channel agonist and antagonist effects of the stereoisomers of the dihydropyridine 202-791.

The effects of the pure stereoisomers of the novel dihydropyridine 202-791 on voltage sensitive calcium channels in nerve and cardiac muscle were examined. The (-)-isomer blocked depolarization-induced uptake of 45Ca2+ into NG108-15 neuroblastoma X glioma cells, blocked the depolarization-induced release of [3H]-norepinephrine from PC12 cells and reduced the Vmax of the slow response action potential recorded from guinea pig papillary muscle. In contrast, the (+)-isomer enhanced these same processes. In papillary muscle, greater enhancement of the slow responses was observed at lower stimulation frequencies. Thus, the (-) and (+) stereoisomers of 202-791 can be shown to be calcium channel antagonist and agonist respectively.

Action Potentials↗
PubMed1985

Characterization of voltage-sensitive calcium channels in a clonal pituitary cell line.

We have pharmacologically characterized voltage sensitive calcium channels (VSCCs) in GH3 cells, an anterior pituitary clonal cell line known to secrete prolactin and growth hormone. Raising the medium K+ concentration from 5 to 50 mM caused an immediate increase in net 45Ca2+ uptake which remained apparent over a 15 minute time course. 45Ca2+ uptake was maximally stimulated nearly 10-fold over basal levels. This K+-induced stimulation of Ca2+ uptake was not prevented by 10-5M tetrodotoxin or by replacing sodium with choline in the assay medium. Ca2+ uptake was, however, inhibited by several VSCC antagonists: nitrendipine, D-600, diltiazem and Cd2+. Further, the novel dihydropyridine VSCC agonists, BAY K8644 and CGP 28392, enhanced 50 mM K+-stimulated 45Ca2+ uptake and these effects were blocked by nitrendipine.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Interaction of steroidal alkaloid toxins with calcium channels in neuronal cell lines.

Depolarization with 50 mM K+ increased 45Ca2+ uptake into neuronal clonal cell lines NG108-15, N1E-115 and NH15-CA2. In each cell line this depolarization-induced uptake was blocked by inorganic and organic blockers of voltage sensitive calcium channels. However, tetrodotoxin (10(-6) M) was ineffective. Moreover, in the presence of tetrodotoxin, neither batrachotoxin nor veratridine inhibited the depolarization-induced uptake. The novel dihydropyridine BAY K8644 enhanced depolarization-induced 45Ca2+ uptake into each cell line in a nitrendipine reversible fashion. In the presence of tetrodotoxin, the BAY K8644/50 mM K+ stimulated uptake could be partially inhibited by batrachotoxin (10(-6) M) and veratridine (5 X 10(-5) M). These effects were not altered by the presence of scorpion venom (1 microgram/ml). The results indicate that both batrachotoxin and veratridine can modulate the effects of dihydropyridines on the gating properties of voltage sensitive calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Dihydropyridine sensitive calcium channels in a smooth muscle cell line.

The pharmacological properties of voltage sensitive calcium channels (VSCC) were examined in a rat aortic smooth muscle cell line (A10). The inorganic VSCC blockers Co2+ and Cd2+ blocked 45Ca2+ uptake into these cells in both 5 mM K+ and 50 mM K+ (depolarizing) conditions. The organic VSCC antagonists nitrendipine, nimodipine, D-600 and diltiazem also blocked 45Ca2+ uptake at low concentrations. The relative potencies of blockade were similar to those found in intact vascular smooth muscle. The VSCC "agonist" BAY K8644 enhanced 45Ca2+ uptake and this effect could be reversed by nitrendipine. These results indicate that A10 cells possess VSCC and that these VSCC behave similarly to those in authentic smooth muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

The pharmacological modification of secretory responses.

Electrolyte transport across the intestinal mucosa can be modulated by several neurotransmitters, hormones and drugs. Opiate agonists and endogenous opioid peptides inhibit electrolyte secretion both in vitro and in vivo. These drugs appear to act at several levels. Thus, opioid effects can be elicited at the local mucosal level. Secondly, antisecretory effects can be demonstrated when opioids are administered into the brain. These central effects appear to involve activation of the sympathetic innervation of the intestine. Thirdly, some antidiarrhoeal drugs such as loperamide may have ancillary non-opiate-like actions that contribute to their effectiveness. In cases of inflammatory bowel disease where local concentrations of inflammatory mediators such as kinins and eicosanoids may be high, non-steroidal anti-inflammatory drugs may be effective in treating diarrhoeal symptoms. The existence of many types of receptors on mucosal cells indicates that several pharmacological approaches exist for the potential modulation of electrolyte transport.

Animals↗