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Biomedical subjects

E Richelson

Publications and source records attributed to E Richelson.

At least 181 records · Page 10Linked to original sources
PubMed1982

Histamine H1 receptors in the brain and spinal cord of the cat.

The regional distribution of histamine H1 receptors in the feline brain and spinal cord was determined in vitro using the radioactively labeled histamine H1 antagonist, [3H]pyrilamine. This distribution of H1 receptors, which was different from that reported for other species, was highest in the hypothalamus and mammillary bodies. Intermediate levels of binding were observed in the cerebral cortical and limbic regions, corpus striatum, colliculi, cerebellum, and medulla. The lowest binding was found in the pons and spinal cord. Binding in the spinal cord was concentrated in the gray matter, but the number of binding sites detected in the dorsal and ventral horns did not differ. The equilibrium dissociation constants for [3H]pyrilamine were similar for the various regions and were in the range of 2--3 nM and the pharmacological characteristics of the feline brain and spinal H1 receptors were similar to those found in the brains of other mammalian species with the exception of the guinea pig.

Animals↗
PubMed1982

High-affinity binding of [3H]doxepin to histamine H1-receptors in rat brain: possible identification of a subclass of histamine H1-receptors.

The binding of the radioactively labeled tricyclic antidepressant, [3H]doxepin, to rat brain tissue was examined. Scatchard plots of specific [3H]doxepin binding indicated the presence of two distinct binding sites. The equilibrium dissociation constant (KD) of the high-affinity site was 0.020 nM with a maximal binding capacity (Bmax) of 13.7 fmol/mg protein. The corresponding values for the high-affinity site were 3.6 nM and 740 fmol/mg protein, respectively. The high-affinity site was sensitive to competition by pharmacologically relevant concentrations of histamine H1 antagonists such as pyrilamine (KD = 1.0 nM), diphenhydramine (KD = 20 nM), d-chlorpheniramine (KD = 1.7 nM), and 1-chlorpheniramine (KD = 97 nM). The Bmax for [3H]doxepin binding to the high-affinity H1-receptor, however, was approximately 10% of the Bmax obtained using [3H]pyrilamine to label the H1-receptor. Various tricyclic antidepressants were very potent inhibitors at the high-affinity [3H]doxepin site. Their potencies, however, did not correlate with their potencies previously reported for the H1-receptor. The regional distribution of [3H]doxepin high-affinity sites correlated with the known distribution of H1-receptors in the rat brain. These results suggest that [3H]doxepin is binding to a subclass of histamine H1-receptors.

Animals↗
PubMed1982

Function and regulation of methionine5-enkephalin and its receptors in murine neuroblastoma cells.

A homogeneous class of enkephalin receptors found in murine neuroblastoma clone N1E-115 (Chang, K.-J., and Cuatrecasas, P. (1979) J. Biol. Chem. 254, 2610-2618) has been confirmed using a centrifugation assay employing cellular membranes. In intact N1E-115 cells, synthetic methionine5-enkephalin inhibited prostaglandin E1-induced intracellular cyclic AMP formation in a naloxone-sensitive manner. Upon demonstrating intracellular methionine5-enkephalin immunocytochemically (Knodel, E., and Richelson, E. (1980) Brain Res. 197, 565-570), analyses of crude N1E-115 extract were made by radioimmunoassay or opiate receptor binding assay following fractionation by molecular sieve chromatography and high pressure liquid chromatography on a mu-Bondapak C18 column. Extracted methionine5-enkephalin immunoreactive material behaved similarly to synthetic methionie5-enkephalin in these analyses. Growth curve studies of the N1E-115 cells indicated that the quantity of methionine5-enkephalin immunoreactive material synthesized per milligram of cellular protein and the maximum number of enkephalin receptor sites per milligram of membrane protein increased as the cells progressed from logarithmic to stationary phase, with no change in the apparent affinity of the enkephalin receptors for [3H]methionine5-enkephalin. These data suggest that adrenergic clone N1E-115 has functional methionine5-enkephalin membrane receptors, that this clone synthesizes methionine5-enkephalin, and that both the enkephalin receptor number and the content of stored methionine5-enkephalin are regulated with respect to cell division.

Alprostadil↗
PubMed1982

Anticholinergic activity of imipramine and some analogs at muscarinic receptors of cultured mouse neuroblastoma cells.

Imipramine and some of its analogs (trimipramine, 3-chlorimipramine, desipramine, 3-chloro-2-hydroxyimipramine, 2-hydroxyimipramine, and didesmethylimipramine), were assayed for their potencies as antimuscarinic agents by their abilities to antagonize muscarinic receptor-mediated cyclic guanosine monophosphate (GMP) formation by cultured mouse neuroblastoma cells. Equilibrium dissociation constants for these compounds yielded the following rank order of potency at the muscarinic receptor: imipramine greater than trimipramine greater than 3-chlorimipramine greater than desipramine greater than 3-chloro-2-hydroxyimipramine greater than 2-hydroxyimipramine greater than didesmethylimipramine. These results indicate that didesmethylation of the side chain nitrogen or hydroxylation of the ring at the 2-position lead to marked reductions (30-fold and 12-fold, respectively) in antimuscarinic activity of imipramine.

Animals↗
PubMed1982

Lack of function of histamine H1 and muscarinic acetylcholine receptors of mouse neuroblastoma cells grown in serum-free medium.

Mouse neuroblastoma cells (Clone NIR-115) were grown in serum-free (defined) medium, defined medium supplemented with serum, and control medium to determine whether serum-free medium could substitute for serum-containing medium in our studies of the histamine H1 and muscarinic acetylcholine receptors of these cells. The function of these receptors as determined by measurement of receptor-mediated cyclic [3H]GMP formation was absent in cells grown in serum-free medium and increased as the percentage of serum was increased in the defined medium, but never attained the levels found with control cells. Muscarinic receptor number for cells grown in defined medium was 60% above that found for control cells with no change in the affinity of the receptor for the radioligand (--)[3H]quinuclidinyl benzilate. Guanylate cyclase and acetylcholinesterase activities for cells grown in defined medium were 23 and 66% of those found in control cells, respectively. This marked reduction of guanylate cyclase activity in large part explains the lack of function of these receptors.

Acetylcholinesterase↗
PubMed1982

Agonist regulation of muscarinic acetylcholine receptors in rat spinal cord.

In vitro studies with cultured cells originating from nervous tissue have shown that chronic exposure to muscarinic agonists results in a loss of muscarinic receptors. To determine whether this type of regulation of muscarinic receptor number also occurs in vivo, we infused carbachol into the spinal cords of rats. A single carbachol injection into the lumbar spinal cord caused a significant increase in the nociceptive threshold. This effect of carbachol diminished to control levels after 12 h of repeated agonist injections every 4 h and was blocked by atropine. The desensitization to the antinociceptive effects of carbachol was associated with a loss of muscarinic receptors as determined by the binding of the muscarinic antagonist [3H]quinuclidinyl benzilate. After a 24-h exposure to carbachol given every 4h, there was about a 60% loss of binding sites. The loss of muscarinic receptors was also blocked by atropine and was reversible. These results represent direct evidence that a muscarinic agonist can regulate receptor number in the central nervous system and suggest that this loss of receptors is associated with a desensitization to the antinociceptive effects of carbachol injected into the spinal cord.

Animals↗
PubMed1982

Changes in the sensitivity of receptors for neurotransmitters and the actions of some psychotherapeutic drugs.

Many types of psychotherapeutic drugs (especially antidepressants) directly and indirectly interact with neurotransmitter receptors, the recognition sites for the chemical messengers released by neurons. These interactions can result in increased or decreased sensitivity of certain receptors. Hypotheses exist to explain some therapeutic and adverse effects of these drugs on the basis of these changes in sensitivity of receptors for neurotransmitters. This paper briefly presents some recently acquired knowledge about these drug-receptor interactions and shows how they can affect the sensitivity of receptors.

Antidepressive Agents, Tricyclic↗
PubMed1982

Perturbation of gastric emptying and duodenal motility through the central nervous system.

This study was undertaken to test the hypothesis that external stimuli acting through the central nervous system perturb the normal gastrointestinal response to meals. Thus, in 4 healthy volunteers we used a multilumen gastroduodenal tube system that allowed simultaneous measurements of gastroduodenal motility, gastric emptying rate, gastric acid secretion, and pancreatic trypsin output. Blood pressure, pulse rate, and skin temperature were also monitored for autonomic response. All subjects were studied on 2 days, receiving on each day two identical test meals. After one of the meals on each day, vertigo was induced by labyrinthine stimulation (ear irrigation with ice water) while the other meal was followed by one of two controls, ear irrigation at 37 degrees C (control stimulation) on 1 day and no stimulation on the other, the order of the tests being randomized. Labyrinthine stimulation at subnauseant levels resulted in a consistent and reproducible delay in gastric emptying of the meal. Further, in 2 of the 4 subjects a marked and reproducible alteration of the postprandial duodenal motility pattern occurred, with a change to one resembling the fasted state, even though nutrients continued to be present in the stomach. Duodenogastric reflux and gastric acid output remained unchanged. Trypsin output decreased initially but later returned to control values. These studies emphasize the role of the central nervous system in the control of gut function after feeding. Labyrinthine stimulation nay be a useful method for investigating inhibitory and disruptive effects of centrally acting stimuli on the human upper gut.

Adolescent↗