Polyamines and uremia.
PAs are intracellular regulators of growth and anabolic processes. Toxic properties of PAs are conferred according to the increasing number of cationic charges. In uremia, PA accumulation occurs both in and outside the cell. Decreased PA synthesis and blunted PA pathway responses suggest PAs may participate in cellular down regulation. This would explain the lack of tissue responses to elevated plasma hormones, a feature of uremia. Such homeostatic control could prevent life-threatening PA toxicity due to an imbalance between production, degradation and excretion. The concurrent rise in plasma PA oxidative activity, while adversely influencing behavior of lymphocytes and neutrophils reduces the likelihood of direct PA toxicity. In addition, preliminary observation of increased glomerular size and capillary area of intact kidneys in PA treated mice suggest there could be a PA dependent adaptive enhancement of renal excretion in circumstances of decreased renal mass due to disease, thus, compensatory renal hypertrophy. It is important to further inspect the non-uremic chronic hyperpolyaminemias as they occur in man. The continued search for parallel adverse systemic and local effects will be useful in strengthening the base for understanding homeostatic consequences of PA accumulation unobserved by the complex mixture of uremic metabolites. In conclusion, we have examined some known regulatory and toxic properties of PAs and related these to features of the uremic syndrome. Available information on the various ramifications of PA dysmetabolism in uremia, as with other suspect toxins, is in part circumscribed and indirect. Caution is to be exercised in evaluating the new and provisional PA related cause and effect relationships suggested here.(ABSTRACT TRUNCATED AT 250 WORDS)
Campbell
R A
RA
Department of Pediatrics, Oregon Health Sciences University, Portland 97201.
D000818:Animals; D005920:Glomerular Mesangium / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D011073:Polyamines / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D014118:Toxins, Biological / Q000378:metabolism*; D014511:Uremia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D011073:Polyamines; D014118:Toxins, Biological