Subtypes of adrenergic receptors and intracellular mechanisms involved in modulatory effects of noradrenaline on glutamate.
We have previously reported that the response of cultured chick cerebellar neurons to glutamate is enhanced by noradrenaline (NA) or isoproterenol and suppressed by clonidine. The present study was carried out to further specify the adrenergic receptor subtypes involved in the facilitatory effect of NA or isoproterenol and the suppressive effect of clonidine, and to examine the intracellular mechanisms underlying these modulatory effects of NA. The clonidine effect, which was mimicked by NA iontophoresed with large ejecting currents, was blocked by yohimbine and tolazoline (alpha 2 antagonists) and also by dibutyryl cyclic AMP or forskolin which augmented the glutamate response by itself. Prazosin, an alpha 1 receptor antagonist did not block the clonidine effect. NA- or isoproterenol-induced facilitation, which was mimicked by denopamine (beta 1 agonist), was antagonized by acebutolol (beta 1 antagonist) and not by ICI 118,551 (beta 2 antagonist). Pretreatment of neurons with pertussis toxin for more than 24 h blocked the suppressive action of clonidine without affecting the facilitatory action of isoproterenol. Furthermore, intracellular injection of GDP beta S inhibited the modulatory effects of either clonidine or isoproterenol. These results indicate that the facilitatory and inhibitory modulatory effects of NA may be mediated by beta 1 and alpha 2 receptors linked to cAMP systems, respectively, and the former is coupled with the stimulatory G protein (Gs) and the latter is with the inhibitory G protein (Gi).
Mori-Okamoto
J
J
Department of Physiology, National Defense Medical College, Tokorozawa, Saitama, Japan.
Namii
Y
Y
Tatsuno
J
J
D000070:Acebutolol / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology*; D002642:Chick Embryo; D003000:Clonidine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004553:Electric Conductivity; D004983:Ethanolamines / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D014043:Tolazoline / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D004983:Ethanolamines; D005971:Glutamates; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D015016:Yohimbine; D018698:Glutamic Acid; D000070:Acebutolol; D014043:Tolazoline; D007545:Isoproterenol; D003000:Clonidine; D000420:Albuterol; C037293:denopamine; D009638:Norepinephrine; D011224:Prazosin