TY - JOUR
T1 - Selective inhibition of cholera toxin and catecholamine stimulated lipolysis by blocking agents
AU - Katz, M. S.
AU - Greenough, W. B.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1975
Y1 - 1975
N2 - Vibrio cholerae enterotoxin stimulates lipolysis in rat epididymal fat cell suspensions. Like hormones this toxin increases adenylate cyclase activity, raising levels of cyclic adenosine 3',5' monophosphate (cAMP), which activates a cellular lipase. Using specific blocking agents, we studied the responses to the adrenergic lipolytic hormones epinephrine, norepinephrine, and isoproterenol, and to cholera toxin. All stimulators were used at 100 x threshold dose. Propranolol (34 μM), a β blocking agent, inhibited epinephrine stimulation (P<0.001) but not that of toxin (P>0.2). Choleragenoid (25 μg/ml), a natural toxoid of cholera toxin, blocked stimulation by toxin (P<0.001) but not that of the adrenergic agents (P>0.2). A β blocker, practolol (3 mM), inhibited stimulation by the catecholamines tested (P<0.005) but not that of toxin (P>0.05). Higher concentrations of propranolol (340 μM) and the α blocking agents phenoxybenzamine (3 mM) and phentolamine (1.6 mM) inhibited all agonists (P<0.001). The response to theophylline was inhibited by all blockers (P<0.05) except propranolol at the lower concentration (34 μM). A combined β and α blockade using propranolol and epinephrine together did not inhibit toxin mediated lipolysis. It appears that stimulation by cholera toxin is independent of β adrenergic receptors. A major inhibition of theophylline mediated lipolysis by α blocking drugs indicated a nonspecific effect of these agents at the concentrations used. The uninhibited response to toxin in the presence of propranolol and epinephrine suggests a lack of relationship of the toxin receptor to either α or β receptors.
AB - Vibrio cholerae enterotoxin stimulates lipolysis in rat epididymal fat cell suspensions. Like hormones this toxin increases adenylate cyclase activity, raising levels of cyclic adenosine 3',5' monophosphate (cAMP), which activates a cellular lipase. Using specific blocking agents, we studied the responses to the adrenergic lipolytic hormones epinephrine, norepinephrine, and isoproterenol, and to cholera toxin. All stimulators were used at 100 x threshold dose. Propranolol (34 μM), a β blocking agent, inhibited epinephrine stimulation (P<0.001) but not that of toxin (P>0.2). Choleragenoid (25 μg/ml), a natural toxoid of cholera toxin, blocked stimulation by toxin (P<0.001) but not that of the adrenergic agents (P>0.2). A β blocker, practolol (3 mM), inhibited stimulation by the catecholamines tested (P<0.005) but not that of toxin (P>0.05). Higher concentrations of propranolol (340 μM) and the α blocking agents phenoxybenzamine (3 mM) and phentolamine (1.6 mM) inhibited all agonists (P<0.001). The response to theophylline was inhibited by all blockers (P<0.05) except propranolol at the lower concentration (34 μM). A combined β and α blockade using propranolol and epinephrine together did not inhibit toxin mediated lipolysis. It appears that stimulation by cholera toxin is independent of β adrenergic receptors. A major inhibition of theophylline mediated lipolysis by α blocking drugs indicated a nonspecific effect of these agents at the concentrations used. The uninhibited response to toxin in the presence of propranolol and epinephrine suggests a lack of relationship of the toxin receptor to either α or β receptors.
UR - http://www.scopus.com/inward/record.url?scp=0016817428&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0016817428&partnerID=8YFLogxK
U2 - 10.1128/iai.12.5.964-968.1975
DO - 10.1128/iai.12.5.964-968.1975
M3 - Article
C2 - 1193734
AN - SCOPUS:0016817428
SN - 0019-9567
VL - 12
SP - 964
EP - 968
JO - Infection and immunity
JF - Infection and immunity
IS - 5
ER -