Back to Search
Start Over
Inhibitory regulation of adenylyl cyclase in the absence of stimulatory regulation. Requirements and kinetics of guanine nucleotide-induced inhibition of the cyc- S49 adenylyl cyclase.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 1983 Nov 10; Vol. 258 (21), pp. 13141-7. - Publication Year :
- 1983
-
Abstract
- cyc- S49 cell membranes contain an adenylyl cyclase activity which is stimulated by forskolin and inhibited by guanine nucleotides and NaF. These inhibitory effects are mediated by an inhibitory guanine nucleotide-binding regulatory component (Ni) affecting the adenylyl cyclase catalytic unit (Hildebrandt, J. D., Sekura, R. D., Codina, J., Iyengar, R., Manclark, C. R., and Birnbaumer, L. (1983) Nature (Lond.) 302, 706-709). Since cyc- S49 cells do not contain a stimulatory guanine nucleotide-binding regulatory component (Ns), these membranes were used to study the requirements and kinetics of activation of Ni in the absence of Ns. Activation of Ni by guanyl-5'-yl imidodiphosphate was time-dependent (i.e. hysteretic) and pseudo-irreversible. Although GTP and guanosine 5'-(beta-thio)diphosphate could prevent the inhibition caused by guanyl-5'-yl imidodiphosphate if added simultaneously with it, they could not reverse the inhibited state induced by previous exposure to guanyl-5'-yl imidodiphosphate. Activation of Ni had an absolute requirement for Mg2+. Unlike the activation of Ns, however, which requires millimolar concentrations of Mg2+ in the absence of hormonal stimulation, activation of Ni requires only micromolar concentrations of the divalent cation. These results support the contention that hormones which activate Ni or Ns do so by altering different parameters of a similar activation mechanism.
- Subjects :
- Animals
Antihypertensive Agents pharmacology
Cell Line
Cell Membrane enzymology
Colforsin
Diterpenes pharmacology
Guanylyl Imidodiphosphate pharmacology
Lymphoma enzymology
Magnesium pharmacology
Manganese pharmacology
Mice
Molecular Weight
Sodium Fluoride pharmacology
Adenylyl Cyclases metabolism
Guanine Nucleotides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 258
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 6685126