Expression of beta 2-adrenoceptors mediating cyclic AMP accumulation in astroglial and neuronal cell lines derived from the rat CNS.
The effect of isoprenaline on cyclic AMP accumulation has been investigated in the rat neuronal cell line B50 and the rat astrocytoma cell line C6. Noradrenaline and isoprenaline stimulated cyclic AMP accumulation in both cell lines. Isoprenaline (0.5 microM; EC50 = 0.1 microM) produced a rapid (T1/2 = 1.3 min) increase in [3H]cyclic AMP accumulation in B50 cells while the response to isoprenaline (0.1 microM; EC50 = 0.01 microM) in C6 cells was somewhat slower (T1/2 = 7.5 min). The response to 0.5 microM isoprenaline was antagonized by both propranolol (IC50 = 8.4 +/- 1.6 nM; N = 3) and the beta 2-selective antagonist ICI 118551 (IC50 = 2.1 +/- 0.2 nM; N = 6). However, no attenuation of the response to isoprenaline (0.5 microM) was observed at concentrations of the beta 1-adrenoceptor antagonist atenolol up to 10 microM (N = 3). In contrast, in C6 cells, which have previously been shown to possess beta 1-adrenoceptors, atenolol inhibited isoprenaline-induced (0.1 microM) cyclic AMP accumulation (IC50 = 2.0 +/- 0.5 microM; N = 6). Furthermore, the beta 2-selective antagonist ICI 118551 was much less potent in the C6 cell line (IC50 = 0.2 +/- 0.05 microM; N = 3) than in the B50 cells. In conclusion, the present data suggest that isoprenaline mediates cyclic AMP accumulation in the neuronal cell line via activation of beta 2-adrenoceptors, while in the astrocytoma cell line the cyclic AMP response is mediated by beta 1-adrenoceptors.
Ruck
A
A
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, U.K.
Millns
P
P
Kendall
D A
DA
Hill
S J
SJ
D000818:Animals; D001254:Astrocytoma / Q000378:metabolism*; D002460:Cell Line / Q000187:drug effects; D002490:Central Nervous System / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D007545:Isoproterenol; D009638:Norepinephrine