Histamine Receptors Mediating a Positive Inotropic Effect in Guinea Pig and Rabbit Ventricular Myocardium: Distribution of the Receptors and Their Possible Intracellular Coupling Processes
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概要
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The difference in histamine receptor subtypes that are involved in the positive inotropic effect of histamine in guinea pig and rabbit ventricular myocardium was analytically characterized. In guinea pig papillary muscles, the positive inotropic effect of histamine was antagonized by cimetidine but not by mepyramine. The converse was true in rabbit papillary muscles. However, histamine evoked a positive inotropic effect through H<SUB>1</SUB>- and H<SUB>2</SUB>-receptors after blockade of H<SUB>2</SUB>- and H<SUB>1</SUB>-receptors in guinea pig and rabbit papillary muscles, respectively. Adenylate cyclase was significantly activated by histamine via H<SUB>2</SUB>-receptors in guinea pig but not in rabbit myocardial ventricular membranes. Accumulation of [<SUP>3</SUP>H]inositol monophosphate in ventricular strips prelabeled with <I>myo</I>-[<SUP>3</SUP>H]inositol was increased by histamine via H<SUB>1</SUB>-receptors to a similar extent in rabbits and guinea pigs. Radioligand binding experiments with [<SUP>3</SUP>H]mepyramine and [<SUP>3</SUP>H]tiotidine showed an increased number of H<SUB>1</SUB>-receptors and a decreased number of H<SUB>2</SUB>-receptors in guinea pig compared with rabbit ventricular myocardium. These results suggest that the positive inotropic effects of histamine are dominated by an H<SUB>1</SUB>-receptor-mediated effect in rabbits and by an H<SUB>2</SUB>-receptor-mediated one in guinea pig ventricular myocardium, and the positive inotropic effect manifested by one subtype apparently restricts the expression of the positive inotropic effect mediated by the other subtype. This species difference is not due to a difference in densities of the receptor subtypes, but may be partly related to a difference in the extents of coupling of H<SUB>2</SUB>-receptors to adenylate cyclase.
著者
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Hattori Yuichi
Department Of Applied Mathematics Faculty Of Science Konan University
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Gando Satoshi
Department Of Anesthesia Sapporo City General Hospital
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Nagashima Masato
Department Of Orthopedic Surgery University Of Occupational And Environmental Health
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Kanno Morio
Department Of Pharmacology Hokkaido University School Of Medicine
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Gando Satoshi
Department of Pharmacology, Hokkaido University School of Medicine
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Hattori Yuichi
Department of Pharmacology, Hokkaido University School of Medicine
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NAGASHIMA Masato
Department of Cellular Physiology and Signal Transduction, Sapporo Medical University
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Nagashima Masato
Department of Pharmacology, Hokkaido University School of Medicine
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