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T Lanthorn

Publications and source records attributed to T Lanthorn.

10 recordsLinked to original sources

The 5-HT3 antagonist tropisetron (ICS 205-930) is a potent and selective alpha7 nicotinic receptor partial agonist.

The 5-HT3 receptor antagonist tropisetron (ICS 205-930) was found to be a potent and selective partial agonist at alpha7 nicotinic receptors. Two other 5-HT3 receptor antagonists, ondansetron and LY-278,584, were found to lack high affinity at the alpha7 nicotinic receptor. Quinuclidine analogues (1 and 2) of tropisetron were also found to be potent and selective partial agonists at alpha7 nicotinic receptors.

Animals↗

Role of peripheral N-methyl-D-aspartate (NMDA) receptors in visceral nociception in rats.

BACKGROUND & AIMS: N-methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels that have an important role in long-term potentiation and memory processing in the central nervous system. The aims in this study were to determine whether NMDA receptors are expressed in the peripheral nervous system and identify their role in mediating behavioral pain responses to colonic distention in the normal gut. METHODS AND RESULTS: Immunohistochemical localization of the NR1 subunit showed that NMDA receptors are expressed on the cell bodies and peripheral terminals of primary afferent nerves innervating the colon. Dorsal root ganglia neurons retrogradely labeled from the colon in short-term culture responded to addition of NMDA with increased intracellular [Ca2+]. Activation of peripheral NMDA receptors in colonic tissue sections caused Ca2+-dependent release of the proinflammatory neuropeptides, calcitonin gene-related peptide and substance P. Behavioral pain responses to noxious mechanical stimulation were inhibited in a reversible, dose-dependent manner by intravenous administration of memantine, a noncompetitive antagonist of the NMDA receptor. Single fiber recordings of decentralized pelvic nerves showed that colorectal distention responsive afferent nerve activity was inhibited by memantine. CONCLUSIONS: Peripheral NMDA receptors are important in normal visceral pain transmission, and may provide a novel mechanism for development of peripheral sensitization and visceral hyperalgesia.

Amino Acid Sequence↗

Study of potency, kinetics of block and toxicity of NMDA receptor antagonists using fura-2.

NMDA receptor antagonists reduced NMDA-triggered increases in [Ca2+]i measured by fura-2 and showed qualitative differences in the potency and kinetics of block. High potency antagonists produced a slow block which allowed an initial increase in [Ca2+]i that was greater than the steady-state level, while compounds with moderate to low potency produced a rapid block that was at steady-state from the first measurement. The more potent antagonists showed the slowest unblocking rates. Using this simple method, novel NMDA antagonists can be screened to ascertain potency, kinetics of block and relative toxicity, prior to animal testing.

Animals↗

Current-to-frequency transduction in CA1 hippocampal pyramidal cells: slow prepotentials dominate the primary range firing.

In order to study how hippocampal pyramidal cells transform a steady depolarization into discharges, CA1 pyramids (n = 32) were injected with 1.5 s long pulses of constant depolarizing current. The firing in response to weak currents was in most cells, characterized by low frequency (0.2-5 Hz), slowly increasing depolarizations preceding each action potential (slow prepotentials, SPPs), a long latency (0.2-5 s) to the initial spike and lack of adaptation. The SPPs, which lasted 30-2,000 ms, showed an increasing steepness with increasing current, and seemed to be a major regulating factor for the slow firing. In response to stronger currents the discharge had a high initial frequency (100-350 Hz), followed by adaptation to steady state firing (5-50 Hz). Thirty of 32 cells showed a dip in the frequency (n = 5), or a pause (n = 25) lasting 250-1,000 ms between the initial burst of firing and the steady state. The pause occurred only at intermediate current strengths. Additional spikes to the initial burst seemed to be recruited through the development of depolarizing waves. The initial slope of these waves resembled those of the SPPs. Similar waves occurred at the expected time of occasionally missing spikes during steady state firing. The variability (SD/mean) of the interspike intervals decreased with increasing frequency of firing. The frequency-current (f/I) relation for the steady state firing showed a simple linear or convex shape, and lacked a secondary range. In contrast, the f/I plots for the initial few interspike intervals had both primary, secondary and tertiary ranges, like motoneurones.

Action Potentials↗