Regulation of the catalytic component of adenylate cyclase. Potentiative interaction of stimulatory ligands and 2',5'-dideoxyadenosine

V. A. Florio, E. M. Ross

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Both adenosine and the P site agent 2',5'-dideoxyadenosine (DDA) reversibly inhibit adenylate cyclase activity in two different preparations of the enzyme that lack the stimulatory guanine nucleotide-binding protein, G/F: plasma membranes from the cyc- variant of S49 lymphoma cells and the resolved catalytic component (C) from rabbit liver. P site agents do not compete with any of the activators of C (Mn2+, G/F, forskolin), nor do they diminish the potency of any activator of C. Rather, activation of C increases the effectiveness of P site agents and causes up to a 10,000-fold increase in the potency of DDA. The ability of G/F or forskolin to potentiate P site inhibition is also noted at concentrations much lower than those required for the stimulation of adenylate cyclase activity. These data are inconsistent with a simple two-state allosteric model for the regulation of the activity of C and demand the postulation of either a distinct, inhibited conformation of the enzyme or the existence of a dead-end complex with adenosine bound to the catalytic site.

Original languageEnglish (US)
Pages (from-to)195-202
Number of pages8
JournalMolecular Pharmacology
Volume24
Issue number2
StatePublished - 1983

Fingerprint

Colforsin
Adenylyl Cyclases
Adenosine
Dideoxyadenosine
Allosteric Regulation
Ligands
Guanine Nucleotides
Enzymes
Lymphoma
Catalytic Domain
Carrier Proteins
Cell Membrane
Rabbits
Liver
2',5'-dideoxyadenosine

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{f8ed8449e8ea46efa201ec20b8f336d7,
title = "Regulation of the catalytic component of adenylate cyclase. Potentiative interaction of stimulatory ligands and 2',5'-dideoxyadenosine",
abstract = "Both adenosine and the P site agent 2',5'-dideoxyadenosine (DDA) reversibly inhibit adenylate cyclase activity in two different preparations of the enzyme that lack the stimulatory guanine nucleotide-binding protein, G/F: plasma membranes from the cyc- variant of S49 lymphoma cells and the resolved catalytic component (C) from rabbit liver. P site agents do not compete with any of the activators of C (Mn2+, G/F, forskolin), nor do they diminish the potency of any activator of C. Rather, activation of C increases the effectiveness of P site agents and causes up to a 10,000-fold increase in the potency of DDA. The ability of G/F or forskolin to potentiate P site inhibition is also noted at concentrations much lower than those required for the stimulation of adenylate cyclase activity. These data are inconsistent with a simple two-state allosteric model for the regulation of the activity of C and demand the postulation of either a distinct, inhibited conformation of the enzyme or the existence of a dead-end complex with adenosine bound to the catalytic site.",
author = "Florio, {V. A.} and Ross, {E. M.}",
year = "1983",
language = "English (US)",
volume = "24",
pages = "195--202",
journal = "Molecular Pharmacology",
issn = "0026-895X",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

TY - JOUR

T1 - Regulation of the catalytic component of adenylate cyclase. Potentiative interaction of stimulatory ligands and 2',5'-dideoxyadenosine

AU - Florio, V. A.

AU - Ross, E. M.

PY - 1983

Y1 - 1983

N2 - Both adenosine and the P site agent 2',5'-dideoxyadenosine (DDA) reversibly inhibit adenylate cyclase activity in two different preparations of the enzyme that lack the stimulatory guanine nucleotide-binding protein, G/F: plasma membranes from the cyc- variant of S49 lymphoma cells and the resolved catalytic component (C) from rabbit liver. P site agents do not compete with any of the activators of C (Mn2+, G/F, forskolin), nor do they diminish the potency of any activator of C. Rather, activation of C increases the effectiveness of P site agents and causes up to a 10,000-fold increase in the potency of DDA. The ability of G/F or forskolin to potentiate P site inhibition is also noted at concentrations much lower than those required for the stimulation of adenylate cyclase activity. These data are inconsistent with a simple two-state allosteric model for the regulation of the activity of C and demand the postulation of either a distinct, inhibited conformation of the enzyme or the existence of a dead-end complex with adenosine bound to the catalytic site.

AB - Both adenosine and the P site agent 2',5'-dideoxyadenosine (DDA) reversibly inhibit adenylate cyclase activity in two different preparations of the enzyme that lack the stimulatory guanine nucleotide-binding protein, G/F: plasma membranes from the cyc- variant of S49 lymphoma cells and the resolved catalytic component (C) from rabbit liver. P site agents do not compete with any of the activators of C (Mn2+, G/F, forskolin), nor do they diminish the potency of any activator of C. Rather, activation of C increases the effectiveness of P site agents and causes up to a 10,000-fold increase in the potency of DDA. The ability of G/F or forskolin to potentiate P site inhibition is also noted at concentrations much lower than those required for the stimulation of adenylate cyclase activity. These data are inconsistent with a simple two-state allosteric model for the regulation of the activity of C and demand the postulation of either a distinct, inhibited conformation of the enzyme or the existence of a dead-end complex with adenosine bound to the catalytic site.

UR - http://www.scopus.com/inward/record.url?scp=0020613837&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020613837&partnerID=8YFLogxK

M3 - Article

VL - 24

SP - 195

EP - 202

JO - Molecular Pharmacology

JF - Molecular Pharmacology

SN - 0026-895X

IS - 2

ER -