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. 1979 Dec;67(4):535–543. doi: 10.1111/j.1476-5381.1979.tb08699.x

Effects of the histamine H2-receptor blocking drugs burimamide and cimetidine on noradrenergic transmission in the isolated aorta of the rabbit and atria of the guinea-pig

MW McCulloch, IC Medgett, MJ Rand
PMCID: PMC2043911  PMID: 229935

Abstract

1 In rabbit aortic strips, concentration-response curves to noradrenaline (NA) were shifted to the right in a parallel and concentration-dependent manner by the α-adrenoceptor blocking drug, phentolamine and also by the histamine H2-receptor blocking drugs, burimamide and cimetidine. Responses to 5-hydroxytryptamine were not affected by these drugs.

2 Burimamide had the properties of a competitive antagonist of noradrenaline, possessing about one-hundredth the potency of phentolamine. Cimetidine was weaker than burimamide and did not fulfil the requirements for competitive antagonism of noradrenaline.

3 In guinea-pig isolated atria, in which noradrenergic transmitter stores were labelled with [3H]-noradrenaline, phentolamine (3 μM), burimamide (30 μM) and cimetidine (30 μM), in decreasing order of effectiveness, each enhanced stimulation-induced efflux of [3H]-noradrenaline, indicating that their blocking effects on prejunctional α-adrenoceptors in this tissue are in the same order of relative potency as on postjunctional α-adrenoceptors in rabbit aortic strips.

4 In the concentrations used (30 μM), neither burimamide nor cimetidine interfered with the neuronal uptake of noradrenaline. Burimamide, and to a much lesser extent, cimetidine, increased the resting efflux of [3H]-noradrenaline from guinea-pig atria.

5 The effect of clonidine, a partial agonist on prejunctional α-adrenoceptors in guinea-pig atria, in increasing stimulation-induced efflux of [3H]-noradrenaline when stimulated with 150 pulses at 5 Hz was blocked by cimetidine (30 μM) and reversed by phentolamine (3 μM) and burimamide (30 μM).

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Selected References

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