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• W2023187052 abstract "Summary— Early substantial evidence of the low susceptibility to β-adrenoceptor antagonists of non α-adrenergic responses reducing gut motility and tone was reluctantly accepted as indicating a third β-receptor subtype different from the β1 and β2. This applied likewise to lipolysis until new selective “lipolytic” β-agonists poorly effective at established β-receptors were introduced. Shortly afterwards these “lipolytic” as well as certain newer and even more selective β-adrenoceptor agonists were shown to be potent inhibitors of intestinal motility. The latter are the “gut-specific” phenylethanolaminotetralins whose availability as pure isomers attested to the stringent stereochemical requirements for selectivity at non-β1, non-β2 β-adrenoceptors. Acceptance of the functionally based concept of a β3-adrenoceptor was boosted on structural grounds by molecular biology studies. Sequence analysis indicated the existence in humans and rodents of genes coding for a third subtype of β-receptor that, when expressed in transfected heterologous cells, had a pharmacological profile distinct from the previously established subtypes. Finally, aryloxypropanolaminotetralins have been prepared as the first selective antagonists of β3-adrenoceptors, thus providing unambiguous conclusive evidence of the distinctive functional features of those abundant in the rat colon. The therapeutic potential in gastroenterology of the newer compounds targetable on the β3-adrenoceptor is suggested by their potent intestinal action in vivo in animal models without any of the cardiovascular or other unwanted effects of conventional β3-adrenoceptor agonists and antagonists, and by the clinically confirmed importance of β-adrenergic control of motor function throughout the alimentary canal. However, open questions include the incidence of species-related differences in β3-adrenoceptors, and as yet there are no data on gastrointestinal functions in humans under the influence of drugs designed to act selectively at these receptors." @default.
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• W2023187052 date "1995-07-08" @default.
• W2023187052 modified "2023-10-17" @default.
• W2023187052 title "β₃-adrenoceptors and intestinal motility" @default.
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• W2023187052 doi "https://doi.org/10.1111/j.1472-8206.1995.tb00507.x" @default.
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