Catecholamine uptake, accumulation, and release in acute porphyria.
Hypertension and tachycardia are well known features of acute porphyria and have been shown to be related to increased circulating catecholamines. The mechanism by which circulating catecholamines are increased was studied using the isolated perfused rat heart and human platelets as a model of adrenergic neuronal function. It was found that neither delta-aminolevulinate (ALA) nor porphobilinogen (PBG) blocked uptake or caused release in the isolated perfused rat heart. Platelets from six patients with acute prophyria, three in remission and three latent, with matching normal controls were studied with regard to their uptake of [(3)H]norepinephrine in the presence of ALA or PBG. It was found that ALA and PBG significantly reduced uptake and accumulation of [(3)H]-norepinephrine in patients with acute porphyria; however, no similar reduction in uptake and accumulation was observed in the platelets of normal controls. Therefore, it appears that there is a latent defect in the catecholamine uptake and (or) accumulation of platelets of patients with acute prophyria which only manifests itself in the presence of ALA or PBG. If platelet uptake serves as a model of adrenergic neuron uptake, this suggests that elevated circulating catecholamine levels during acute attacks of acute porphyria are caused at least partially by blockade of re-uptake into the sympathetic neurons.
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000622:Aminolevulinic Acid / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002395:Catecholamines / Q000097:blood / Q000378:metabolism*; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000097:blood; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D011162:Porphobilinogen / Q000494:pharmacology; D011164:Porphyrias / Q000097:blood / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats
D002395:Catecholamines; D011189:Potassium Chloride; D011162:Porphobilinogen; D000622:Aminolevulinic Acid; D011163:Hydroxymethylbilane Synthase; D009638:Norepinephrine