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Your search keyword '"Walsh, R. E."' showing total 2 results
Start Over Author "Walsh, R. E." Publisher american society for pharmacology and experimental therapeutics
2 results on '"Walsh, R. E."'

1. Preferential binding of the novel prostaglandin SC-46275 to canine gastric versus intestinal receptors.

Author

Tsai BS, Keith RH, Perkins WE, Walsh RE, Anglin CP, Collins PW, Gasiecki AW, Bauer RF, Jones PH, and Gaginella TS

Subjects
Alprostadil metabolism, Alprostadil pharmacology, Animals, Anti-Ulcer Agents pharmacology, Cells, Cultured, Dogs, Female, Gastric Acid metabolism, Gastric Mucosa drug effects, Gastric Mucosa metabolism, Intestinal Mucosa drug effects, Intestinal Mucosa metabolism, Intestine, Small drug effects, Intestine, Small metabolism, Male, Misoprostol metabolism, Misoprostol pharmacology, Muscle, Smooth metabolism, Muscle, Smooth ultrastructure, Radioligand Assay, Stomach drug effects, Tritium, Alprostadil analogs & derivatives, Anti-Ulcer Agents metabolism, Intestine, Small ultrastructure, Receptors, Prostaglandin E metabolism, Stomach ultrastructure
Abstract

Prostaglandins (PGs) in the E-series exhibit potent gastric antisecretory activity, but can also cause diarrhea, which is mediated via PGE receptors. SC-46275, an omega-chain cyclopentenyl analog of the E-type PG enisoprost, was evaluated with other E-PGs for PGE receptor binding activity in gastric and intestinal tissues. SC-46275, enisoprost, misoprostol and PGE1 were first evaluated in enriched canine gastric parietal cells with [3H]misoprostol free acid binding and subsequently with [3H]PGE1 binding in canine intestinal tissues where misoprostol free acid had weak receptor binding activity. The receptor binding potency of SC-46275 (IC50, 0.013 mM) in enriched canine parietal cell preparations was found to be much greater than misoprostol and enisoprost (IC50, 10 and 8 nM), whereas PGE1 had the least potency (IC50, 37 nM). Similar relative potencies for these PGs were also obtained in the inhibition of histamine-stimulated acid secretion in enriched parietal cell preparations. In small intestinal mucosal and muscle membranes, the receptor binding potency of SC-46275 (IC50, 13 and 20 microM) was much less than misoprostol or enisoprost (IC50, 0.39-1.2 microM) and substantially less than PGE1 (IC50, 0.017 and 0.066 microM). This weak binding activity of SC-46275 in intestinal tissues is consistent with its reported weak diarrheagenic activity in the rat. These results suggest that SC-46275 binds preferentially to gastric vs. intestinal PGE receptors and is specific for the EP3 receptors.

Published
1995

2. Multiple actions of the leukotriene B4 receptor antagonist SC-41930.

Author

Villani-Price D, Yang DC, Walsh RE, Fretland DJ, Keith RH, Kocan G, Kachur JF, Gaginella TS, and Tsai BS

Subjects
Animals, Dinoprostone biosynthesis, Eicosanoids biosynthesis, Epoxide Hydrolases drug effects, Guinea Pigs, Humans, Leukemia, Experimental drug therapy, Leukemia, Experimental metabolism, Leukemia, Experimental pathology, Leukemia, Myeloid drug therapy, Leukemia, Myeloid metabolism, Leukemia, Myeloid pathology, Leukotriene B4 biosynthesis, Leukotriene B4 metabolism, Neutrophils drug effects, Neutrophils metabolism, Phospholipases A drug effects, Phospholipases A2, Prostaglandin-Endoperoxide Synthases drug effects, Receptors, Leukotriene B4, Skin drug effects, Skin metabolism, Superoxides metabolism, Tumor Cells, Cultured, Benzopyrans pharmacology, Receptors, Immunologic antagonists & inhibitors
Abstract

7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro-8- propyl-2H-1-benzopyran-2-carboxylic acid (SC-41930), a leukotriene B4 (LTB4) receptor antagonist with anti-inflammatory activity in animal models of colitis, was evaluated for effects on superoxide, LTB4 and prostaglandin E2 production. SC-41930 inhibited human neutrophil (PMN) superoxide generation maximally stimulated by f-Met-Leu-Phe (IC50 4 microM) and C5a (IC50 approximately 12 microM). Moreover, postreceptor stimulation of superoxide production by NaF (a G protein activator), but not by phorbol myristate acetate, was significantly inhibited by SC-41930, indicating that SC-41930 may act via attenuation of a G protein-mediated signal transduction. SC-41930 also inhibited A23187-stimulated LTB4 production (IC50 5.3 microM) in human PMN as well as LTB4 (IC50 2.1 microM) and prostaglandin E2 (IC50 2.9 microM) production in HL-60 cells. When coinjected intradermally (400 micrograms/site), SC-41930 inhibited A23187-stimulated increases in LTB4 levels in guinea pig skin. SC-41930 inhibited human synovial phospholipase A2 (IC50 72 microM), A23187-stimulated 5-hydroxy-eicosatetranoic acid production in human PMN (IC50 8.5 microM), and rat peritoneal leukotriene A4 hydrolase (IC50 20 microM), but not ram seminal vesical cyclooxygenase. The results suggest that the anti-inflammatory activity of SC-41930 could be attributed to postreceptor inhibition of inflammatory mediator production by PMN and other cells in addition to antagonism of PMN LTB4 receptors.

Published
1992

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