TY - JOUR
T1 - Homologous and heterologous β-adrenergic desensitization in hepatocytes. Additivity and effect of pertussis toxin
AU - Hernández-Sotomayor, S. M Teresa
AU - Macías-Silva, Marina
AU - Plebañski, Magdalena
AU - García-Sáinz, J. Adolfo
PY - 1988/12/9
Y1 - 1988/12/9
N2 - In hepatocytes obtained from hypothyroid rats, phorbol myristate acetate (PMA) and vasopressin diminished the accumulation of cyclic AMP and the stimulation of ureagenesis induced by isoprenaline or glucagon without altering significantly the accumulation of cyclic AMP induced by forskolin. Pretreatment with PMA markedly reduced the stimulation of ureagenesis and the accumulation of cyclic AMP induced by isoprenaline or glucagon. In membranes from cells pretreated with PMA, the stimulation of adenylate cyclase induced by isoprenaline + GTP, glucagon + GTP or by Gpp[NH]p were clearly diminished as compared to the control, whereas forskolin-stimulated activity was not affected. The data indicate heterologous desensitization of adenylate cyclase. It was also observed that the homologous (García-Sáinz J.A. and Michel, B. (1987) Biochem. J. 246, 331-336) and this heterologous β-adrenergic desensitizations were additive. Pertussis toxin treatment markedly reduced the heterologous desensitization of adenylate cyclase but not the homologous β-adrenergic desensitization. It is concluded that the homologous and heterologous desensitizations involve different mechanisms. The homologous desensitization seems to occur at the receptor level, whereas the heterologous probably involves the guanine nucleotide-binding regulatory protein, Ns.
AB - In hepatocytes obtained from hypothyroid rats, phorbol myristate acetate (PMA) and vasopressin diminished the accumulation of cyclic AMP and the stimulation of ureagenesis induced by isoprenaline or glucagon without altering significantly the accumulation of cyclic AMP induced by forskolin. Pretreatment with PMA markedly reduced the stimulation of ureagenesis and the accumulation of cyclic AMP induced by isoprenaline or glucagon. In membranes from cells pretreated with PMA, the stimulation of adenylate cyclase induced by isoprenaline + GTP, glucagon + GTP or by Gpp[NH]p were clearly diminished as compared to the control, whereas forskolin-stimulated activity was not affected. The data indicate heterologous desensitization of adenylate cyclase. It was also observed that the homologous (García-Sáinz J.A. and Michel, B. (1987) Biochem. J. 246, 331-336) and this heterologous β-adrenergic desensitizations were additive. Pertussis toxin treatment markedly reduced the heterologous desensitization of adenylate cyclase but not the homologous β-adrenergic desensitization. It is concluded that the homologous and heterologous desensitizations involve different mechanisms. The homologous desensitization seems to occur at the receptor level, whereas the heterologous probably involves the guanine nucleotide-binding regulatory protein, Ns.
KW - Adenylate cyclase
KW - Homologous-heterologous desensitization
KW - Pertussis toxin
KW - Phorbol esters
KW - Protein kinase C
KW - β-Adrenoceptor
UR - http://www.scopus.com/inward/record.url?scp=0024243880&partnerID=8YFLogxK
U2 - 10.1016/0167-4889(88)90207-8
DO - 10.1016/0167-4889(88)90207-8
M3 - Article
C2 - 2848590
AN - SCOPUS:0024243880
VL - 972
SP - 311
EP - 319
JO - BBA Molecular Cell Research
JF - BBA Molecular Cell Research
SN - 0167-4889
IS - 3
ER -