cap alpha. /sub 2/-Adrenergic receptor-mediated sensitization of forskolin-stimulated cyclic AMP production

Journal Article · Sun Mar 01 04:00:00 EST 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.5.1294· OSTI ID:6125005

Jones, S B; Toews, M L; Turner, J T; Bylund, D B

Preincubation of HT29 human colonic adenocarcinoma cells with ..cap alpha../sub 2/-adrenergic agonists resulted in a 10- to 20-fold increase in forskolin-stimulated cyclic AMP production as compared to cells preincubated without agonist. Similar results were obtained using either a (/sup 3/H)adenine prelabeling assay or a cyclic AMP radioimmunoassay to measure cyclic AMP levels. This phenomenon, which is termed sensitization, is ..cap alpha../sub 2/-adrenergic receptor-mediated and rapid in onset and reversal. Yohimbine, an ..cap alpha../sub 2/-adrenergic receptor-selective antagonist, blocked norepinephrine-induced sensitization, whereas prazosin (..cap alpha../sub 1/-adrenergic) and sotalol (..beta..-adrenergic) did not. The time for half-maximal sensitization was 5 min and the half-time for reversal was 10 min. Only a 2-fold sensitization of cyclic AMP production stimulated by vasoactive intestinal peptide was observed, indicating that sensitization is relatively selective for forskolin. Sensitization reflects an increased production of cyclic AMP and not a decreased degradation of cyclic AMP, since incubation with a phosphodiesterase inhibitor and forskolin did not mimic sensitization. Increasing the levels of cyclic AMP during the preincubation had no effect on sensitization, indicating that sensitization is not caused by decreased cyclic AMP levels during the preincubation. This rapid and dramatic sensitization of forskolin-stimulated cyclic AMP production is a previously unreported effect that can be added to the growing list of ..cap alpha../sub 2/-adrenergic responses that are not mediated by a decrease in cyclic AMP.

• Research Organization: Univ. of Missouri, Columbia
• OSTI ID: 6125005
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:5; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADENINES
ADRENAL HORMONES
AMINES
AMP
ANIMAL CELLS
ANIMALS
ANTIMETABOLITES
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
BIOCHEMISTRY
BIOSYNTHESIS
CARCINOMAS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CHEMISTRY
DISEASES
DRUGS
HETEROCYCLIC COMPOUNDS
IMMUNOASSAY
IMMUNOLOGY
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MAN
MEMBRANE PROTEINS
NEOPLASMS
NEUROREGULATORS
NORADRENALINE
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PRIMATES
PROTEINS
PURINES
RADIOASSAY
RADIOIMMUNOASSAY
RADIOIMMUNOLOGY
RECEPTORS
SYMPATHOLYTICS
SYMPATHOMIMETICS
SYNTHESIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUMOR CELLS
VERTEBRATES