A comparison of pre- and postsynaptic effects of alpha-adrenolytic drugs in the pulmonary artery of the rabbit

Borowski, E.; Starke, K.; Ehrl, H.; Endo, T.

Neuroscience 2(2): 285-296


ISSN/ISBN: 0306-4522
PMID: 20591
DOI: 10.1016/0306-4522(77)90095-1
Accession: 068518199

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Strips of the main pulmonary artery of the rabbit were preincubated with 3H-noradrenaline [norepinephrine, NA] and then superfused and electrically stimulated transmurally. Yohimbine, dihydroergotamine and tolazoline at low concentrations enhanced the stimulation-evoked overflow of 3H; up to 100 times higher concentrations were needed to reduce stimulation-evoked contractions. Piperoxan and mianserin enhanced the evoked overflow and reduced the evoked contractions at identical concentrations. Phentolamine, azapetine, clozapine and phenoxybenzamine at low concentrations diminished the contractile response; up to 30 times higher concentrations were needed to increase the evoked 3H overflow. At high concentrations all drugs accelerated basal 3H outflow. Separation of individual 3H-compounds revealed that a high concentration of piperoxan markedly accelerated the basal outflow of 3H-3,4-dihydroxyphenylglycol. Lower concentrations of piperoxan and yohimbine that did not affect the basal efflux of 3H-compounds greatly increased the evoked overflow of 3H-NA as well as 3H-3,4-dihydroxyphenylglycol and 3H-normetanephrine. The pulmonary artery contains postsynaptic .alpha.-adrenoceptors which mediated smooth muscle contractions. Its NA neurons possessed presynaptic .alpha.-receptors which mediated inhibition of the per pulse release of NA by a negative feedback mechanism. .alpha.-Adrenolytic drugs varied widely in their relative pre- and postsynaptic effects. Yohimbine, dihydroergotamine and tolazoline preferentially blocked presynaptic .alpha.-receptors and at low concentrations selectively facilitated NA release. Phentolamine, azapetine, clozapine and phenoxybenzamine preferentially blocked postsynaptic .alpha.-receptors and at low concentrations selectively antagonized the contractile response. Piperoxan and mianserin occupied an intermediate position. In a given tissue, pre- and postsynaptic .alpha.-receptors may differ in their structure.