Abstract
A study was made of the activation of rat erythrocyte adenyl cyclase by dopamine, D(-)-norepinephrine, and their N-methyl and N-isopropyl derivatives. The concentrations required for 50% maximal stimulation (ED50) for norepinephrine, epinephrine, and isoproterenol were 5, 0.69, and 0.24 µM, respectively. For dopamine, N-isopropyldopamine, and N-methyldopamine the ED50 values were 84, 8, and 6.8 µM. While the maximum stimulation achieved with norepinephrine and its N-alkylated derivatives was the same, that for dopamine and its derivatives varied with potency. It was postulated that the D(-)-configuration of the β-hydroxylated series, in contrast to the deoxy analogues, induced a more activating conformational change in the cyclase. This was supported by the finding that L(+)-isoproterenol was equipotent with N-isopropyldopamine. Propranolol, chlorpromazine, haloperidol, phentolamine, serotonin, and phenoxybenzamine inhibited to the same extent the stimulation of adenyl cyclase produced by N-methyldopamine and norepinephrine. At low concentrations of inhibitor the stimulation by norepinephrine, but not by dopamine, could be reduced. These observations, along with the inactivity of apomorphine as a stimulator of adenyl cyclase, negate the existence of a specific dopamine receptor associated with the rat erythrocyte adenyl cyclase.
- Copyright ©, 1971, by Academic Press, Inc.
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|