1. In rat isolated tail arteries and atria in which transmitter stores are labelled with (3H)-noradrenaline, isoprenaline in low concentrations facilitates the stimulation-induced efflux of tritium. 2. This effect is dependent on the frequency and duration of electrical stimulation, being observed only at low frequency (2 Hz) and short duration (10 s in atria and 30 s in arteries) or at high frequency (5 Hz) and long duration (1 min in atria and 4 min in arteries). 3. In atria, phenotlamine enchances tritium efflux with stimulation at 5 Hz for 1 min but not at 2 Hz for 10 s. Conversely, propranolol reduces tritium efflux with stimulation at 2 Hz for 10 s but not at 4 Hz for 1 min. 4. The results can be interpreted in terms of the selective operation, depending on the frequency and duration of electrical stimulation, of inhibitory and facilitatory feedback loops for transmitter release involving prejunctional alpha -and beta-adrenoceptors, respectively.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Quantitative structure-activity relationships of imidazolidine derivatives related to clonidine at peripheral alpha-adrenoceptors.

The effects of clonidine, oxymetazoline and thirteen substituted phenyliminoimidazolidine analogues of clonidine were studied and compared on postjunctional alpha-adrenoceptors in guinea-pig and rabbit aorta and on prejunctional alpha-adrenoceptors in guinea-pig atria. In the aorta all compounds were partial agonists at postjunctional alpha-adrenoceptors. Correlation of agonist potency with various combinations of their physicochemical parameters showed that, with the present series of compounds, physicochemical parameters alone determined 92% of the variance in the data with potency being primarily and highly correlated with pKa. Similarly in atria, all compounds, with the possible exceptions of St 95 and St 1943, appeared to be partial agonists at prejunctional alpha-adrenoceptors; transmitter noradrenaline release could either be inhibited (field stimulation at 1 Hz for 5 s) or enhanced (5 Hz for 30 s). The results indicate that 2,6-substitution in the phenyl ring appears to be a specific non-physicochemical activity-enhancing factor at prejunctional but not postjunctional alpha-adrenoceptors. A comparison with data in the literature giving the acute hypotensive potencies of the compounds suggests that central alpha-adrenoceptors may more closely resemble atrial prejunctional alpha-adrenoceptors than aortic postjunctional alpha-adrenoceptors. Quantitative correlations between centrally-mediated hypotensive and peripheral vasoconstrictor effects of clonidine-like imidazolidines do not provide a sufficiently sensitive method of distinguishing between alpha-adrenoceptor subtypes.

Animals↗

PubMedDate not supplied

Effects of some catecholamines on noradrenergic transmission in the rabbit ear artery.

1. The effects of noradrenaline, adrenaline, isoprenaline, dopamine and the N-methyl and alpha-methyl homologoues of dopamine were studied on tritium release and on vasoconstrictor responses to sympathetic nerve stimulation in isolated arteries of the rabbit ear after labelling noradrenergic transmitter stores with 3H-noradrenaline. These observations were made in the presence of cocaine (100 muM). 2. Noradrenaline (0-5 and 5 muM) inhibited transmitter release and abolished vasoconstrictor responses. A concentration of 0-05 muM had no effect on transmitter release, although the vasoconstrictor response was reduced and there was sometimes a vasodilator response. 3. Adrenaline in concentrations of 0-05, 0-5 and 5 muM decreased transmitter release and vasoconstrictor responses; sometimes there was a vasodilator response. 4. Isoprenaline in concentrations of 0-05, 0-5 and 5 muM did not affect transmitter release. Vasoconstrictor responses were either unaffected or enhanced by all concentrations of isoprenaline when infusions had been in progress for 15 min; but immediately after beginning the infusion of 5 muM isoprenaline, the response was reduced. 5. Dopamine (0-05, 0-5 and 5 muM) produced a concentration-dependent decrease in transmitter release, but vasoconstrictor responses were not reduced with infusions of 0-05 or 0-5 muM; during infusions of 5 muM, stimulation produced a vasodilator response.

Animals↗