Increased Serum Copper in Pulmonary Hypertension: Involvement of Thromboxane?

Dr. Joshua Backon, Brookman Clinic, POB 16336, Jerusalem (Israel) Dear Sir: References Ahmed and Sackner [1985] have recently reported increased serum copper in primary pulmonary hypertension and suggested involvement of the α-adrenergic system, especially as dopamine/1⁄8ydrox-ylase, is copper dependent. I would like to suggest that thromboxane could be involved and is regulated by copper levels. Thromboxane is involved in pulmonary hypertension [Frolich et al., 1980]. The distribution of copper is unbalanced in the brain and is more concentrated in the left hemisphere [Delva, 1970]. Since copper acts as a coenzyme of dopamine-ß-hy-droxylase, which converts dopamine into noradrenaline, there is a higher level of noradrenaline in the left hemisphere [Mys-lobodsky and Weiner, 1978; Oke et al., 1978]. In the pineal, neural stimulation causes the release of noradrenaline which elevates pineal-N-acetyltransferase which controls melatonin production [Namboodiri et al., 1981] and this formation of melatonin is markedly stimulated by noradrenaline [Brownstein and Axelrod, 1974]. Since melatonin is necessary for the thromboxane (TXA2) receptor to be in the active state, increased melatonin can raise TXA2 levels [Horrobin et al., 1980]. Thus, the two concepts of increased serum copper and increased thromboxane can be linked via effects on melatonin production. Ahmed, T.; Sackner, M.A.: Increased serum copper in primary pulmonary hypertension: a possible pathogenic link? Respiration 47: 243-246 (1985). Brownstein, M.; Axelrod, J.: Pineal gland: 24-hour rhythm in norepinephrine turnover. Science 184: 163-165(1974). Delva, V.A.: in Petelin, Extrapyramidal hyperkine-sis. (Medizine, Moscow 1970). Frolich, J.C.; Ogletree, M.; Peskar, B.A.; Brigham, K.L.: Pulmonary hypertension correlated to pulmonary thromboxane synthesis; in Samuelsson, Ramwell, Paoletti, Advances in prostaglandin and thromboxane research, vol. 7 (Raven Press, New York 1980). Horrobin, D.F.; Manku, M.S.; Oka, M.; et al.: Selective control of formation of 1 and 2 series pros-taglandins: a new concept in the regulation of inflammation and immunity. Future Trends in Inflammation, Royal College of Surgeons, London 1980 (MTP Press, Lancaster). Myslobodsky, M.; Weiner, M.: Clinical psychology in the chemical environment. Psychol. Rep. 43: suppl., pp. 247-276 (1978). Namboodiri, M.A.; Favilla, J.; Klein, D.C: Pineal N-acetyltransferase is inactivated by disulphide-containing peptides: insulin is the most potent. Science 213: 571-573(1981).