Differential role of protein kinase C in desensitization of muscarinic receptor induced by phorbol esters and receptor agonists
PKC, a phorbol ester receptor, copurified with specific binding sites of ({sup 3}H)phorbol-12,13,-dibutyrate (({sup 3}H)PDBu). The specific binding of ({sup 3}H)PDBu to intact cells was saturable to a single class of binding sites. The PKC and phorbol ester receptors in N1E-115 cells can be down regulated by prolonged phorbol ester incubation. Phorbol 12-myristate 13-acetate (PMA) suppressed muscarinic receptor-mediated cyclic GMP response in a time-dependent and a concentration-dependent fashion and the suppressive effect of PMA could be attenuated by a protein kinase inhibitor, H-7, as well as by down-regulation of the PKC through long-term incubation with PDBu. Exposure of the cells to the muscarinic agonist carbamylcholine also desensitized subsequent CBC-mediated cyclic GMP response. However, pretreatment with carbamylcholine did not desensitize histamine-induced cyclic GMP formation while treatment with PMA suppressed this histamine-mediated response. Preincubation of the cells with CBC, but not with phorbol ester, resulted in down-regulation of muscarinic receptors. The loss of muscarinic receptors induced by agonist even occurred when the phosphoinositide hydrolysis response was suppressed.
- Research Organization:
- Maryland Univ., Baltimore, MD (USA)
- OSTI ID:
- 6612860
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
PARASYMPATHOMIMETICS
RECEPTORS
PHORBOL ESTERS
BIOLOGICAL EFFECTS
PHOSPHOTRANSFERASES
BIOLOGICAL FUNCTIONS
BIOCHEMICAL REACTION KINETICS
MICE
TIME DEPENDENCE
TISSUE DISTRIBUTION
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUMOR CELLS
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
CARCINOGENS
DISTRIBUTION
DRUGS
ENZYMES
ESTERS
FUNCTIONS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
PROTEINS
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RODENTS
TRANSFERASES
VERTEBRATES
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