K. Fecho et al., EVIDENCE FOR BETA-ADRENERGIC-RECEPTOR INVOLVEMENT IN THE IMMUNOMODULATORY EFFECTS OF MORPHINE, The Journal of pharmacology and experimental therapeutics, 265(3), 1993, pp. 1079-1087
The present study assessed the involvement of the beta adrenergic syst
em in the immunomodulatory effects of morphine. Male Lewis rats were a
dministered either the nonselective beta adrenergic antagonist nadolol
, the beta1-selective adrenergic antagonist atenolol or the beta2-sele
ctive adrenergic antagonist (7-methylindan-4-yloxy)-3-isopropylaminobu
tan-2-ol (ICI-118,551) in doses of 0, 0.125, 0.5, 2.0 or 8.0 mg/kg s.c
. before the administration of 15 mg/kg morphine or saline s.c. After
sacrifice, the spleen was removed and blood was collected from each ra
t and multiple in vitro immune assays were performed. Pretreatment wit
h all three beta adrenergic antagonists completely antagonized the sup
pressive effects of morphine on the proliferative responses of splenic
leukocytes to concanavalin-A (Con-A), phytohemagglutinin (PHA), lipop
olysaccharide (LPS) and the combination of ionomycin and phorbol myris
tate acetate (PMA). None of the antagonists blocked the suppressive ef
fects of morphine on the proliferative responses of blood leukocytes t
o concanavalin-A or phytohemagglutinin, splenic natural killer (NK) ce
ll activity, total splenic leukocyte counts and blood leukocyte counts
per milliliter. These results demonstrate the involvement of beta adr
energic receptors in certain of morphine's immunosuppressive effects.
Moreover, because both nadolol and atenolol are peripherally acting co
mpounds, these data implicate peripheral beta adrenergic receptors spe
cifically in morphine's immunomodulatory effects.