Ontogeny of beta-adrenergic receptor-mediated cyclic AMP generating system in primary cultured neurons.
The developmental changes in the beta-adrenergic receptor/cyclic AMP generating system were examined using mouse cerebral cortical neurons in primary culture. During neuronal growth in vitro, the number of binding sites for [3H]dihydroalprenolol (DHA) showed a tendency to increase (Bmax), while the affinity (Kd) for [3H]DHA did not show any noticeable changes. Basal and isoproterenol-stimulated adenylate cyclase activities as well as the activation of adenylate cyclase by 5'-guanylylimidodiphosphate (GppNHp), NaF and forskolin showed progressive and parallel increases during neuronal growth on a polylysine-coated surface. The treatment of primary cultured neurons with islet-activating protein (IAP), one of the pertussis toxins, attenuated the inhibitory effect of carbachol, a muscarinic agonist, on isoproterenol-induced activation of adenylate cyclase activity. These results indicate that primary cultured neurons possess a cyclic AMP generating system coupled with beta-adrenergic and muscarinic receptors, which is regulated via stimulatory and inhibitory GTP-binding proteins, respectively. The results described above also suggest that the beta-adrenergic receptor, stimulatory and inhibitory types of GTP-binding proteins and adenylate cyclase may develop in a parallel fashion during neuronal growth on a polylysine-coated surface.
Ma
F H
FH
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Ohkuma
S
S
Kishi
M
M
Kuriyama
K
K
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000375:Aging; D000818:Animals; D001921:Brain / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004082:Dihydroalprenolol / Q000378:metabolism*; D005333:Fetus; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012969:Sodium Fluoride / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D011943:Receptors, Adrenergic, beta; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D004082:Dihydroalprenolol; D012969:Sodium Fluoride; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases; D007545:Isoproterenol