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Release of [ 3 H]‐noradrenaline from the sympathetic nerves to bovine mesenteric lymphatic vessels and its modification by α‐agonists and antagonists
Author(s) -
Allen J.M.,
McCarron J.G.,
McHale N.G.,
Thornbury K.D.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11593.x
Subject(s) - prazosin , yohimbine , rauwolscine , phentolamine , stimulation , tetrodotoxin , methysergide , chemistry , postsynaptic potential , idazoxan , endocrinology , medicine , antagonist , receptor
1 Isolated segments of bovine mesenteric lymphatic vessels were loaded with [ 3 H]‐noradrenaline and its efflux in response to field stimulation examined. Vessels were attached to an isometric force transducer for the simultaneous recording of mechanical activity. 2 Field stimulation at 1, 4 and 8 Hz (0.3 ms pulses, 1 min train) increased spontaneous contraction rate and evoked 3 H release up to a maximum of 4.5% of total tissue 3 H at 8 Hz. Output per pulse was maximal at 4 Hz. 3 Tetrodotoxin (3 × 10 −6 m ) blocked the release of 3 H in response to field stimulation although the drug did not attenuate release evoked by high K + (65 m m ) solution. Field‐evoked release of 3 H was also absent in Ca 2+ ‐free solution containing EGTA (1 m m ). 4 When vessels were preincubated with labelled transmitter plus cocaine (5 × 10 −5 m ) evoked release of 3 H was absent. After preloading with [ 3 H]‐noradrenaline, cocaine (10 −6 m ) potentiated both the mechanical response to field stimulation and evoked 3 H release. 5 The relatively non selective α‐adrenoceptor antagonist phentolamine (3 × 10 −6 m ) and the α 2 ‐antagonists yohimbine (10 −8 m ) and rauwolscine (10 −6 m ) significantly increased evoked 3 H release at both of the frequencies examined (1 and 4 Hz). In contrast, the selective α 1 ‐antagonist prazosin (10 −6 m ) failed to alter 3 H release to 4 Hz stimulation although release at 1 Hz was potentiated in the presence of the drug. 6 The postsynaptic excitatory response to field stimulation remained in the presence of prazosin (10 −6 m ), but was converted to an inhibitory effect in the presence of phentolamine (3 × 10 −6 m ), yohimbine (10 −6 m ) or rauwolscine (10 −6 m ). 7 Evoked 3 H efflux was significantly reduced by clonidine (10 −6 m ), xylazine (10 −6 m ) and exogenous noradrenaline (5 × 10 −7 m ), although phenylephrine (10 −6 m ) reduced release only at the lower of the two frequencies tested (1 Hz). 8 These findings suggest that release of 3 H by field stimulation reflects endogenous transmitter release and that this is subject to autoinhibition via feedback onto inhibitory prejunctional α 2 ‐adrenoceptors. The postjunctional excitatory response is mediated via postjunctional α 2 ‐adrenoceptors.