Summary
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1.
The uptake of radiolabelled 14C-histamine into guinea-pig isolated left atria was determined.
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2.
Mepyramine up to 10−7 M had no significant effect upon the uptake of total radioactivity. Metiamide (10−4 M) produced a small but not significant inhibition of uptake. SK & F 91581 (10−4 M) and amodiaquine (10−4 M) both significantly inhibited uptake by 48.2±4.2 and 56.7±1.2% respectively.
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3.
The metabolism profiles of radiolabelled histamine after 5 and 30 min incubation were examined by thin-layer chromatography.
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4.
SK & F 91581 (10−4 M) and amodiaquine (10−4 M) reduced the proportion of Nτ-methyl-histamine and acid metabolites after a 30 min incubation. The levels of unmetabolized histamine were elevated. This may explain their inhibitory action upon histamine uptake.
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5.
The effects of mepyramine, metiamide, SK & F 91581 and amodiaquine were then examined upon the positive inotropic and chronotropic responses of isolated left and right atria to histamine.
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6.
Mepyramine (10−7 M) inhibited the positive inotropic responses only (H1), whereas metiamide (10−4 M) inhibited the positive chronotropic responses only (H2). SK & F 91581 (10−4 M) had no effect upon these responses and amodiaquine (10−5 M) depressed the maxima of the rate response dose-response curves.
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7.
The relationship between uptake and metabolism of histamine and its pharmacological response is discussed.
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Broadley, K.J., Wilson, C., Smith, I.R. et al. Uptake and metabolism of histamine in guinea-pig isolated atria and their relationship to the pharmacological responses. Naunyn-Schmiedeberg's Arch. Pharmacol. 315, 155–161 (1980). https://doi.org/10.1007/BF00499258
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DOI: https://doi.org/10.1007/BF00499258