Norepinephrine mediated uncoupling of alpha/sub 1/-adrenergic receptors from phosphoinositide hydrolysis is rapid and separate from the down-regulation of the receptors
The authors have studied the regulation of the coupling of alpha/sub 1/ receptor binding sites to inositide hydrolysis in primary neuronal cultures prepared from the brain stem and hypothalamus of neonatal Wistar-Kyoto rats. Cultures were exposed to norepinephrine (NE) and the NE stimulated phosphatidylinositol (PI) response or binding of (/sup 125/I)HEAT to alpha/sub 1/ recognition sites was determined. Exposure of neurons to 10 ..mu..M NE for 2 hr decreases stimulated PI hydrolysis by 70-80%, whereas alpha/sub 1/ receptor number and affinity are unchanged at this time. Further stimulation of the cultures results in a down-regulation of receptor number with a maximal loss of 50% binding sites after a 24 hr pretreatment. The uncoupled NE stimulated PI response after a 2 hr pretreatment with NE returns to 80-90% of control 4 hr after removal of the NE. Down-regulated alpha/sub 1/receptor binding sites after 24 hr of pretreatment with NE return after a 72 hr washout period, and the effect is blocked by cycloheximide (3.6 ..mu..M). These results suggest that stimulation of alpha/sub 1/ receptors causes a rapid uncoupling of the receptor from PI hydrolysis and that the response returns to normal in a matter of hours. In contrast, the return of receptors following down-regulation requires much longer times and appears to involve other mechanisms.
- Research Organization:
- Univ. of Florida School of Medicine, Gainesville
- OSTI ID:
- 6859387
- Report Number(s):
- CONF-8604222-; TRN: 87-010348
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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NERVE CELLS
RATS
TRACER TECHNIQUES
ADRENAL HORMONES
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
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NUCLEI
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ORGANIC PHOSPHORUS COMPOUNDS
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550201* - Biochemistry- Tracer Techniques