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.
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 alpha-adrenoceptor blocking drug, phentolamine and also by the histamine H(2)-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 [(3)H]-noradrenaline, phentolamine (3 muM), burimamide (30 muM) and cimetidine (30 muM), in decreasing order of effectiveness, each enhanced stimulation-induced efflux of [(3)H]-noradrenaline, indicating that their blocking effects on prejunctional alpha-adrenoceptors in this tissue are in the same order of relative potency as on postjunctional alpha-adrenoceptors in rabbit aortic strips.4 In the concentrations used (30 muM), neither burimamide nor cimetidine interfered with the neuronal uptake of noradrenaline. Burimamide, and to a much lesser extent, cimetidine, increased the resting efflux of [(3)H]-noradrenaline from guinea-pig atria.5 The effect of clonidine, a partial agonist on prejunctional alpha-adrenoceptors in guinea-pig atria, in increasing stimulation-induced efflux of [(3)H]-noradrenaline when stimulated with 150 pulses at 5 Hz was blocked by cimetidine (30 muM) and reversed by phentolamine (3 muM) and burimamide (30 muM).
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000294:innervation; D002049:Burimamide / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D011817:Rabbits; D009435:Synaptic Transmission / Q000187:drug effects*; D013890:Thiourea / Q000031:analogs & derivatives*
D006146:Guanidines; D002927:Cimetidine; D013890:Thiourea; D003042:Cocaine; D002049:Burimamide; D009638:Norepinephrine; D010646:Phentolamine