Morphine-induced desensitization and down-regulation at mu-receptors in 7315C pituitary tumor cells

Journal Article · Sun Jan 01 00:00:00 EST 1989 · Life Sciences; (USA)

DOI:https://doi.org/10.1016/0024-3205(89)90548-1· OSTI ID:6994839

Puttfarcken, P S; Cox, B M ^[1]

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1. Uniformed Services Univ. of the Health Sciences, Bethesda, MD (USA)

Pituitary 7315c tumor cells maintained in culture were treated with varying concentrations of morphine from 10 nM to 300 {mu}M, for periods of five or forty-eight hours. The ability of the mu-opioid receptor agonist, DAMGO, to inhibit forskolin-stimulated adenylyl cyclase in washed membrane preparations from the treated cells was compared with its activity in membranes from cells incubated in the absence of added morphine. In the same membrane preparations, the number and affinity of mu-opioid receptors was estimated by measurements of ({sup 3}H)diprenorphine binding. After 5 hr of treatment with morphine concentrations of 100 nM or higher, a significant reduction in inhibition of adenylyl cyclase by DAMGO was observed. Little further loss of agonist activity was observed when the incubations were extended to 48 hr. After 5 hr of morphine treatment, there was no change in either the number of receptors, or their affinity for ({sup 3}H)diprenorphine. However after 48 hr of morphine treatment, greater than 25% reductions in receptor number were apparent with morphine pretreatment concentrations of 10 {mu}M or higher. These results suggest that opioid tolerance in this system is primarily associated with a reduced ability of agonist-occupied receptor to activate the effector system. Receptor down-regulation was not necessary for loss of agonist response, although a reduction in receptor number occurred after exposure to high concentrations of morphine for periods longer than 5hr.

• OSTI ID: 6994839
• Journal Information: Life Sciences; (USA), Vol. 45:20; ISSN 0024-3205
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CYCLASES
ENZYME ACTIVITY
ENDORPHINS
RECEPTORS
MORPHINE
BIOCHEMICAL REACTION KINETICS
CELL CULTURES
CELL MEMBRANES
INHIBITION
PITUITARY GLAND
TRITIUM COMPOUNDS
TUMOR CELLS
ALKALOIDS
ANALGESICS
ANIMAL CELLS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
ENDOCRINE GLANDS
ENZYMES
GLANDS
HYDROGEN COMPOUNDS
KINETICS
LYASES
MEMBRANE PROTEINS
MEMBRANES
NARCOTICS
NEUROREGULATORS
OPIUM
ORGANIC COMPOUNDS
ORGANS
PROTEINS
REACTION KINETICS
550201* - Biochemistry- Tracer Techniques