The effects of mercuric chloride on calmodulin-mediated Ca2+ transport in rat brain.
We have shown previously that mercuric chloride (HgCl2) inhibits in vitro vasopressin release from the isolated rat neurohypophysis with maximum inhibition occurring with 0.5 mM HgCl2. Associated with the inhibition of hormone release is an increase in 45Ca+2 uptake, an increase in cytosolic 45Ca+2, and a reduction of 45Ca+2 accumulation by mitochondria in the intact gland. In the present series of studies, the effect of HgCl2 on calmodulin (CM) function in neural tissue preparations is reported. Mercuric chloride (0.5 mM) reduced 45Ca+2 binding to CM purified from bovine neurohypophyses by 20% and inhibited endogenous CM-stimulated Ca,Mg-ATPase activity from rat brain mitochondria in a dose-dependent fashion. Ca,Mg-ATPase activity was inhibited by 50 and 80% with 0.5 and 5.0 mM HgCl2, respectively. CM-stimulation of Ca,Mg-ATPase activity was inhibited by calmidazolium (CMZ) with maximal inhibition seen with 0.1 mM CMZ. Reversibility of the HgCl2 interaction with CM was demonstrated using CM-stimulated phosphodiesterase (PDEase) activity from rat brain. HgCl2 inhibited both basal and CM-stimulated PDEase activity in a dose-dependent manner with maximum inhibition occurring with 1.0 mM HgCl2. Preexposure of CM to an inhibitory concentration (1.0 mM) of HgCl2 resulted in no loss of stimulatory PDEase enzyme activity. From these results, we conclude that HgCl2 reversibly interferes with 45Ca+2 binding to CM and also inhibits CM-regulated Ca+2 pumping enzyme systems in the neurohypophysis. The inhibition of vasopressin release from the intact gland in the presence of HgCl2 thus, may be associated with a disruption of calcium in the neurohypophysis.
Clifton
G G
GG
Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Oelsner
D
D
Anderson
C R
CR
Pearce
C J
CJ
Wallin
J D
JD
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002147:Calmodulin / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008627:Mercuric Chloride / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D002132:Calcium Radioisotopes; D002147:Calmodulin; D007093:Imidazoles; C031938:calmidazolium; D008627:Mercuric Chloride; D010727:Phosphoric Diester Hydrolases; D000252:Calcium-Transporting ATPases; D002118:Calcium