TY - JOUR
T1 - Effect of lithium on prostaglandin E1- stimulated adenylate cyclase activity of human platelets
AU - Yao-Chun, Wang
AU - Pandey, Ghanshyam N.
AU - Mendels, Joe
AU - Frazer, Alan
N1 - Funding Information:
* This investigation was supported in part by research funds from the Veterans Administration and NIH grant HL-01813. A preliminary report of part of this work appeared in Clin. Res. 21, 265 (1973). $ The work presented here is in partial fulfillment of the requirements for the degree of Doctor of Philosophy. Department of Pharmacology. University of Pennsylvania. $ Affective Diseases Research Unit, Veterans Administration Hospital, Philadelphia, Pa. 19104. 8 Departments of Pharmacology and Psychiatry, University of Pennsylvania, School of Medicine.
PY - 1974/2/15
Y1 - 1974/2/15
N2 - The effect of lithium (Li) on the stimulation of adenylate cyclase by prostaglandin E1(PGE1) was examined. In platelet sonicates, Li, as well as sodium (Na), potassium (K), and rubidium (Rb) significantly reduced the PGE1-induced stimulation of adenylate cyclase in a dose-dependent manner. The inhibition due to Rb was significantly less than that produced by the other cations; at a high concentration, 64 mM, Li was a more potent inhibitor than the other cations. In intact platelets, only Li reduced the PGE1-enhanced accumulation of [3H]cyclic AMP, K and Rb being ineffective. As little as 1 mM Li significantly reduced the stimulatory effect of PGE1 on [3H]cyclic AMP production in this sytem. The inhibition produced by Li was not blocked by phentolamine, whereas phentolamine did block the inhibition due to norepinephrine (NE). Magnesium enhanced the stimulatory effect of PGE1 on the production of labeled cyclic AMP in intact platelets and antagonized the inhibition produced by Li on this process. These data show that Li antagonizes PGE1- induced stimulation of platelet adenylate cyclase at a site distinct from that at which NE acts.
AB - The effect of lithium (Li) on the stimulation of adenylate cyclase by prostaglandin E1(PGE1) was examined. In platelet sonicates, Li, as well as sodium (Na), potassium (K), and rubidium (Rb) significantly reduced the PGE1-induced stimulation of adenylate cyclase in a dose-dependent manner. The inhibition due to Rb was significantly less than that produced by the other cations; at a high concentration, 64 mM, Li was a more potent inhibitor than the other cations. In intact platelets, only Li reduced the PGE1-enhanced accumulation of [3H]cyclic AMP, K and Rb being ineffective. As little as 1 mM Li significantly reduced the stimulatory effect of PGE1 on [3H]cyclic AMP production in this sytem. The inhibition produced by Li was not blocked by phentolamine, whereas phentolamine did block the inhibition due to norepinephrine (NE). Magnesium enhanced the stimulatory effect of PGE1 on the production of labeled cyclic AMP in intact platelets and antagonized the inhibition produced by Li on this process. These data show that Li antagonizes PGE1- induced stimulation of platelet adenylate cyclase at a site distinct from that at which NE acts.
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U2 - 10.1016/0006-2952(74)90215-9
DO - 10.1016/0006-2952(74)90215-9
M3 - Article
C2 - 4363215
AN - SCOPUS:0015954796
SN - 0006-2952
VL - 23
SP - 845
EP - 855
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 4
ER -