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Stimulation of presynaptic beta-adrenoceptors enhances [3H]-noradrenaline release druing nerve stimulation in the perfused cat spleen.

Abstract：

:1 The effects of isoprenaline, propranolol and phosphodiesterase inhibitors on (3)H-transmitter overflow elicited by low frequency nerve stimulation were determined in the isolated perfused spleen of the cat.2 (-)-Isoprenaline (0.14, 1.4, and 14 nM) produced a concentration-dependent increase in [(3)H]-transmitter overflow evoked by nerve stimulation at 1 Hz and was more effective at 1 Hz than at 2 hertz.3 A concentration of propranolol (0.1 muM), devoid of neurone blocking activity, blocked this effect of (-)-isoprenaline. These results are compatible with the presence of beta-adrenoceptors in the noradrenergic nerve endings of the cat spleen.4 (+)-Isoprenaline (140 nM) failed to increase the release of radioactivity induced by nerve stimulation, indicating that the beta-adrenoceptor mediating the facilitation of transmitter release was stereospecific.5 The increase in (3)H-transmitter overflow induced by nerve stimulation during exposure to the phosphodiesterase inhibitor, papaverine (27 muM) was more pronounced than that obtained in the presence of 3-isobutyl-1-methyl xanthine (IBMX) 0.5 mM. The facilitation in transmitter release induced by papaverine was not correlated with the granular effect produced by this drug.6 In the presence of papaverine, the concentration-effect curve for (-)-isoprenaline on transmitter release was shifted to the left and its maximum was increased. In addition, propranolol significantly reduced the enhancement in noradrenaline release obtained by exposure to papaverine under conditions in which the granular effect produced by the phosphodiesterase inhibitor was even greater than in the absence of the beta-blocker.7 It is concluded that activation of presynaptic beta-adrenoceptors in the perfused cat spleen leads to an enhancement in transmitter release which appears to be linked to an increase in cyclic adenosine 3',5'-monophosphate levels in noradrenergic nerve endings.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Celuch SM,Dubocovich ML,Lander SZ

doi

10.1111/j.1476-5381.1978.tb07779.x

subject

Has Abstract

pub_date

1978-05-01 00:00:00

pages

97-109

issue

eissn

0007-1188

issn

1476-5381

journal_volume

pub_type

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Stimulation of presynaptic beta-adrenoceptors enhances [3H]-noradrenaline release druing nerve stimulation in the perfused cat spleen.