Phorbol ester stimulates secretory activity while inhibiting receptor-activated aminopyrine uptake by gastric glands
Both cyclic AMP-dependent and -independent secretagogues stimulate pepsinogen release, respiration and H/sup +/ secretory activity (AP uptake) in rabbit gastric glands. 12-O-tetradecanoylphorbol-13-acetate (T), a diacyglycerol analog, activates protein kinase C (PKC) and stimulates secretion in many systems. T stimulated respiration and pepsinogen release by glands and increased AP uptake by both glands and purified parietal cells. However, T reduced AP uptake by glands stimulated with carbachol (C) or histamine (H) with an apparent IC/sub 50/ of 1 nM. Preincubation with T for 30 min produced maximum inhibition which was not reversed by removal of T. T accelerated the decline of the transient C peak while the late steady state response to H was most inhibited. H-stimulated AP uptake was also inhibited by 50 ..mu..g/ml 1-oleoyl-2-acetyl-glycerol, a reported PKC activator, but not by the inactive phorbol, 4..cap alpha..-phorbol-12,13-didecanoate. In contrast, T potentiated AP uptake by glands stimulated with submaximal doses of dibutyryl cyclic AMP. These results suggest inhibition by T is a specific effect of PKC activators. The differing effects of T on secretion indicators may result from a dual action of T on receptor and post-receptor intracellular events.
- Research Organization:
- Morehouse School of Medicine, Atlanta, GA
- OSTI ID:
- 6840057
- Report Number(s):
- CONF-8604222-
- 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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Related Subjects
ANTIPYRINE
UPTAKE
PEPSIN
SECRETION
PHORBOL ESTERS
BIOLOGICAL EFFECTS
AMP
GASTROINTESTINAL TRACT
GLANDS
INHIBITION
PHOSPHOTRANSFERASES
RABBITS
ACID PROTEINASES
ANIMALS
ANTIPYRETICS
AZOLES
BODY
CARCINOGENS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DIGESTIVE SYSTEM
DRUGS
ENZYMES
ESTERS
HETEROCYCLIC COMPOUNDS
HYDROLASES
MAMMALS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PEPTIDE HYDROLASES
PHOSPHORUS-GROUP TRANSFERASES
PYRAZOLES
PYRAZOLINES
TRANSFERASES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology