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Biomedical subjects

E G Anderson

Publications and source records attributed to E G Anderson.

At least 73 records · Page 4Linked to original sources
PubMed1990

5-HT1 receptor agonists reduce the Ca+ component of sensory neuron action potentials.

Serotonin (5-HT) agonists, selective for 5-HT1, 5-HT2 or 5-HT3 receptor subtypes, were tested for their ability to mimic 5-HT in narrowing the tetraethylammonium-induced calcium-dependent plateau of action potentials recorded from frog sensory neurons. 5-Carboxamidotryptamine, 5-HT, alpha-methyl 5-HT and 5-methoxy-tryptamine possessed full agonist activity, with EC50S of 19 nM, 210 nM, 3.7 microM and 1.7 microM, respectively. 2-Methyl 5-HT was inactive. This agonist profile indicates that the calcium-dependent plateau in these sensory somata is modulated by a 5-HT1-like receptor.

5-Methoxytryptamine↗
PubMed1990

5-HT2 and 5-HT3 receptors mediate two distinct depolarizing responses in rat dorsal root ganglion neurons.

The effects of serotonin (5-HT) were studied on transmembrane potentials in 188 rat dorsal root ganglion cells (150 A-type, 16 C-type and 22 unidentified neurons). 5-HT produced a concentration-dependent depolarization in 88% of these neurons. Membrane input resistance (Rin), determined from the slope of current-voltage displacement curves, was increased in 51% and decreased in 41% of the responding neurons. Both responses occurred in 8% of the neurons. No differences in these responses were observed between A- and C-type neurons. Norepinephrine (NE) depolarized 75% (n = 20) of the neurons tested while increasing the Rin. In cells where 5-HT decreased Rin, 2-methyl 5-HT, but not alpha-methyl 5-HT, mimicked the response. The selective 5-HT3 antagonist, ICS 205-930, blocked this response, but ketanserin and methiothepin did not affect it. The 5-HT-induced increase in Rin was blocked by 5-HT2 antagonists (ketanserin, methiothepin and spiperone); mimicked by alpha-methyl 5-HT, but not affected by 2-methyl 5-HT. The selective 5-HT3 antagonist, ICS 205-930, did not antagonize this response. The action of NE but not 5-HT was blocked by the selective alpha 1 antagonist, prazosin. These data indicate that the 5-HT induced depolarization with decreased Rin is mediated by 5-HT3 receptors and the depolarization with increased Rin is mediated by 5-HT2 receptors. Furthermore, these two receptors can occur on the same cell.

Animals↗
PubMed1990

5-HT3 receptors modulate spinal nociceptive reflexes.

The selective 5-HT3 receptor agonist 2-methyl-serotonin (2-Me-5-HT) mimicked the antinociceptive activity of 5-HT when intrathecally administered to rats. Two hundred micrograms (i.t.) doses of these agonists produced similar increases in tail flick latency. However, equal doses of 2-Me-5-HT and 5-HT doubled and tripled, respectively, the mean response latency as measured by the hot plate test. The potent and selective 5-HT3 receptor antagonists ICS 205-930 (3-tropanyl-indole-3-carboxylate) and MDL 72222 (3-tropanyl-3,5-dichlorobenzoate) antagonized the antinociceptive effects of both 5-HT and 2-Me-5-HT. However, there were differences in the efficacy of these antagonists. Thus, intrathecal pretreatment with ICS 205-930 (0.05 micrograms) or MDL 72222 (0.1 micrograms) blocked the antinociceptive effects of 5-HT (200 micrograms, i.t.) as measured by the tail flick test, however, higher doses (0.1 and 1.0 micrograms, respectively) were required in the hot plate test. Pretreatment with ICS 205-930 (0.1 microgram) or MDL 72222 (0.1 microgram) blocked the effects of 2-Me-5-HT (200 micrograms, i.t.) in both analgesiometric tests. It is concluded that 5-HT3 receptors are intimately involved in the modulation of spinal nociceptive responses.

Animals↗
PubMed1990

Fatigue fractures of the foot.

While fatigue fractures are common in military practice they are much less so in civilian practice and thus tend to be overlooked. Fractures occur most commonly in the distal second and third metatarsal shafts and within the calcaneum, but occur in almost any other bone of the foot. Any suspicious history of repetitive stress or sudden change in activity, athletic or otherwise, associated with swelling and point tenderness warrants further investigation by bone scintigraphy. Attention is drawn to the importance of understanding the basic biomechanical function of the foot and how it may affect the development of fatigue fractures. A distinction is drawn between the distal fractures of the second and third metatarsal shafts and those occurring in the proximal shafts of any of the metatarsals which have a different aetiology. Following conventional management in a plaster cast, it is suggested that any biomechanical anomaly which is present is compensated appropriately with an orthotic insole.

Foot Injuries↗
PubMed1990

Competitive and noncompetitive N-methyl-D-aspartate antagonists modify hypoxia-induced membrane potential changes and protect rat hippocampal slices from functional failure: a quantitative comparison.

Hippocampal slice survival after hypoxia was improved by exposure to competitive and noncompetitive N-methyl-D-aspartate (NMDA) antagonists. The rapid blockade and reappearance of synaptic transmission during hypoxia was not altered by these antagonists. However, [(+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d] cyclohepten-5, 10-imine maleate (MK-801) (50 microM) and 2-amino-5-phosphonopentanoic acid (dl-AP5) (25 microM) delayed the disappearance of these reactivated orthodromic population spikes. Intracellular recordings showed that MK-801 and dl-AP5 delayed the late, but not early, hypoxic depolarization of pyramidal cells, and improved recovery of membrane potential and input resistance (Rin) in many cells after reoxygenation. No untreated cells showed recovery. Thus, both competitive and noncompetitive NMDA antagonists decreased the hypoxia-induced depolarization and Rin. With the return of evoked population spikes as an index for recovery from hypoxia, the ED50 values for dl-AP5, MK-801, phencyclidine and dextromethorphan were 7.7, 4.5, 7.1 and 75 microM, respectively. Thus, in contrast to their higher affinities for the NMDA receptor MK-801 and phencyclidine were not significantly more potent than dl-AP5 in protecting hippocampal slices from hypoxia, and isobolographic analysis revealed dose-additive interactions. The unexpectedly low potency of the noncompetitive NMDA antagonists in protecting against hypoxia is attributed to magnesium in the buffer and the hypoxia-induced membrane depolarization, both of which have been shown to reduce the effectiveness of noncompetitive NMDA antagonists.

2-Amino-5-phosphonovalerate↗
PubMed1990

Pharmacological characterization of 5-hydroxytryptamine2 and 5-hydroxytryptamine3 receptors in rat dorsal root ganglion cells.

5-Hydroxytryptamine (5-HT) depolarized 87% of the rat dorsal root ganglion cells recorded. 5-HT increased the input resistance (Rin) in 50%, decreased Rin in 41% and produced both responses in 9% of the responding cells. When 5-HT increased the Rin, the response was mimicked by the 5-HT2 agonists alpha-methyl-5-HT, (+/-)-1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane HCl, quipazine and MK 212 (6-chloro-1-[1-piperazinyl]-pyrazine), but not by 2-methyl-5-HT or carboxamidotryptamine. The response to 5-HT was antagonized by ketanserin, spiperone and methiothepin. The unsurmountable blockade induced by higher concentrations of ketanserin was not explained by pseudo-irreversible antagonism or multiple receptor subtypes, but could result from a two-state receptor model or multiple subtypes of the 5-HT2 receptor. This conclusion is supported by the partial agonist action of DOI. Cells responding to 5-HT with depolarization and decreased Rin responded similarly to 2-methyl-5-HT and phenylbiguanide, but not to alpha-methyl-5-HT or carboxyamidotryptamine. This response was surmountably blocked by ICS 205-930 (3-tropanyl-indole-3-carboxylate) (pA2 = 10.3) and MDL 72222 (3-tropanyl-3,5-dichlorobenzoate)(pA2 = 7.8). The arylpiperazines, quipazine and MK 212, antagonized the action of 2-methyl-5-HT with IC50 values of 8 and 4 nM, respectively. These data indicate that 5-HT2 receptors mediate the increased Rin and 5-HT3 receptors mediate the decreased Rin.

Animals↗
PubMed1989

Glucose and sulfonylureas modify different phases of the membrane potential change during hypoxia in rat hippocampal slices.

Intracellular recording during hypoxia in submerged hippocampal slices revealed an initial hyperpolarization with decreased membrane input resistance followed by complete depolarization. Glibenclamide (1 microM) reduced and tolbutamide (400 microM) completely blocked the hypoxic hyperpolarization and the accompanying increase in conductance. Neither glibenclamide nor tolbutamide altered the time to 25 or 50% depolarization. Sulfonylurea-treated slices completely depolarized during 10 min of hypoxia and did not recover upon reoxygenation. In contrast, 11 mM glucose had no effect on hypoxic hyperpolarization or conductance, but it significantly slowed hypoxic depolarization. In half of the intracellular recordings made during high glucose hypoxia, the membrane potential and input resistance returned during reoxygenation. Extracellular recordings were used to evaluate the effect of sulfonylureas and high glucose on acute neuronal survival from hypoxia. Glibenclamide (0.1-5 microM) did not change the survival rate of slices exposed to hypoxia, whereas, high glucose (11 and 40 mM) dramatically improved the recovery of population spikes during reoxygenation. These findings support the hypothesis that an ATP-sensitive K+ channel mediates hypoxic hyperpolarization, but these channels are not regulated by glucose in the brain as in pancreatic islet-cells. These results also suggest that high glucose protects hippocampal slices from hypoxia by slowing the hypoxia-induced depolarization.

Action Potentials↗
PubMed1989

Serotonin modulates calcium-dependent plateau of action potentials recorded from bull frog A-type sensory neurons which is omega-conotoxin GVIA-sensitive, but dihydropyridine-insensitive.

Tetraethylammonium-treated bull frog sensory neurons exhibit a calcium-dependent plateau on the falling limb of the action potential, which is reduced in duration by 5-HT. The portion of the calcium-dependent plateau which is reduced by 5-HT is blocked by omega-conotoxin GVIA but is not reduced by nifedipine or enhanced by Bay K 8644. The lack of effect of 5-HT, when retested after exposure of a previously 5-HT sensitive neuron to conotoxin favors the hypothesis that 5-HT reduces the duration of the calcium-dependent plateau by inactivating voltage-dependent calcium channels, rather than by increasing a voltage-dependent potassium current.

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