Circulating Pool and Adrenal Soluble Content of Dopamine B-Hydroxylase (DBH), in Rats, Guinea Pigs, Dogs and Humans: Their Role in Determining Acute Stress-lnduced Changes in Plasma Enzyme Levels'

Abstract

Cubeddu, L. X., Y. R. Barbella, A. Marrero, J. Trifaro and A.S, lsrael: Circulating pool and adrenal soluble content of dopamine & hydroxylase (DBH), in rats, guinea pigs, dogs and humans: Their role in determining acute stress-induced changes in plasma enzyme levels. J. Pharmacol. Exp, Ther. 2111 271-279, 1579. Dogs and rats anesthetized with pentobarbital were subiected to an acute hemorrhagic-hypotensive slress. ln both spec¡es, the reduction of blood pressure to 40 mm Hg for 60 min, produced a 5- to 8-fold increase in plasma epinephrine, whereas the plasma dopamine É-hydroxylase (DBH) concentration and its specific activity was augmented only in dogs (2.5 times above basal levels). Similarly anesthetized rats and guinea pigs were injected with sal¡ne or crystalline insulin (5 U/kg b.wt. s.c.). ln both species, 2 hr after insulin injection,there was a 6096 reduction in the blood glucose levels and a 5-to lGfold ¡ncrease in plasma epinephrine. The plasma DBH concentration and specitic activity was augmented only in guinea pigs (4 times above basal levels). The basal plasma DBH concentrations were 21.9, 6.6 and 2.4 nmol/hrlml, in rats, guinea pigs and dogs, respectively. The total plasma DBH activity (nanomoles per hour) was much greater in dogs ( 1843 a 1 51) than ¡n rats (240 t 38) and guinea p¡gs (1 23 i 19). The total DBH activity present in two adrenal glands was 36,424,12,029 and 435 nmol/hr in dogs, guinea pigs and rats, respectively. Guinea pigs had the highesl proportion (55%) of soluble DBH ¡n chromatfin granules. ln rats and dogs, only 25% of the enzyme was found in the soluble form. Theretore, the total soluble ("releasable") DBH (nanomoles per hour)in adrenal glands was: 99 i '10 in rats, 6666 a 70'1 in guinea pigs and 9979 t 1941 in dogs. The followinq ratios of adrenal soluble DBH,/total plasma DBH, were obtained: 0.5, 5 and 63, in rats, dogs and guinea p¡gs, respectively. The higher the ratio, the greater the poss¡bility ot seeing increases in plasma DBH during acute stresses which augment the adrenal medullary discharge. Plasma OBH was measured in 17 normotensive, apparently healthy subiecls, and adrenal glands were obtained from recently autopsied bodies. The human plasma DBH concentralion was 1108 a 163 nmol/hr,/ml and the total plasma DBH activity averaged 2812 pmollhr. The total adrenal DBH activity was 226 t I 6,imol/hr and 51 .3 a 4.2% of the enzyme was in the soluble form. Humans had the lowest ratio of adrenal soluble DBH,/total plasma DBH (0.O4). From these results one could predict that acute stresses which increase the aclivity of the adrenal medulla would induce marked changes in plasma DBH in guinea pigs, moderate changes in dogs, minimal changes in rats and none in humans.