Regulation of muscarinic acetylcholine receptors in cultured guinea pig pancreatic acini
Regulation of muscarinic receptors in cultured guinea pig pancreatic acini was investigated by assessing the effects of cholinergic agonists on binding of (N-methyl-TH)scopolamine ((TH)NMS) and on amylase release. Freshly dispersed acini bound (TH)NMS with a K/sub d/ of 74 pM and a maximal binding level (B/sub max/) of 908 fmol/mg DNA. Carbachol (CCh) stimulated amylase secretion and inhibited (TH)NMS binding. Incubation of acini for 30 min with 0.1 mM CCh decreased the subsequent efficacy of CCh in stimulating amylase release by threefold but had no effect on its potency. In contrast, amylase release in response to cholecystokinin octapeptide (CCK-8) was not altered by CCh preincubation. (TH)NMS binding to acini was decreased only 15-20% after 30-min incubation with CCh. However, culture of acini with 0.1 mM CCh decreased (TH)NMS binding by 50% at 3-4 h and by 85-90% at 24 h. This decrease was attributable primarily to a reduction in B/sub max/ (TH)NMS binding also was decreased to a similar extent by the cholinergic agonists bethanechol and methacholine but not by other secretagogues. The decrease in antagonist binding induced by CCh was dose dependent, with the IC50, 5.8 M, approximating the EC50 for amylase release, 4.3 M. Cultured of acini for 24 h with CCh abolished subsequent amylase release in response to CCh but not to CCK-8. The results indicate that muscarinic receptor turnover in the pancreatic acinus is regulated by receptor activation and that both a decease in receptor numbers and sensitivity to agonists follows prolonged cholinergic agonist exposure.
- Research Organization:
- Univ. of California, San Francisco, CA
- OSTI ID:
- 6283243
- Journal Information:
- Am. J. Physiol.; (United States), Vol. 251:1
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AMINES
RADIORECEPTOR ASSAY
AMYLASE
SECRETION
PANCREAS
PHYSIOLOGY
ACETYLCHOLINE
ANIMAL CELLS
CELL CULTURES
GUINEA PIGS
RECEPTORS
TRITIUM COMPOUNDS
AMMONIUM COMPOUNDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
DIGESTIVE SYSTEM
DRUGS
ENDOCRINE GLANDS
ENZYMES
ESTERS
GLANDS
GLYCOSYL HYDROLASES
HYDROLASES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NEUROREGULATORS
O-GLYCOSYL HYDROLASES
ORGANIC COMPOUNDS
ORGANS
PARASYMPATHOMIMETICS
QUATERNARY COMPOUNDS
RODENTS
TRACER TECHNIQUES
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics
551001 - Physiological Systems- Tracer Techniques