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Involvement of pertussis toxin‐sensitive and ‐insensitive mechanisms in α‐adrenoceptor modulation of noradrenaline release from rat sympathetic neurones in tissue culture
Author(s) -
Hill C.E.,
Powis D.A.,
Hendry I.A.
Publication year - 1993
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.1476-5381.1993.tb13806.x
Subject(s) - pertussis toxin , toxin , adrenergic receptor , adrenergic , endocrinology , sympathetic nervous system , norepinephrine , tyramine , medicine , sympathetic nerve , chemistry , receptor , electrophysiology , neuroscience , biology , pharmacology , g protein , stimulation , biochemistry , dopamine , blood pressure
1 Sympathetic neurones derived from superior cervical ganglia of neonatal rats and maintained in tissue culture were used to investigate the modulation of neurotransmitter release by presynaptic receptors. Three week old cultures of neurones were loaded with [ 3 H]‐noradrenaline to label endogenous neurotransmitter stores. Release of noradrenaline was evoked by depolarization with raised extracellular K + in the presence of desipramine and corticosterone to prevent uptake of released catecholamine. 2 Potassium (55 mmol 1 −1 ) depolarization for 30 s caused more than a four fold increase in 3 H overflow from basal levels but this increase was reduced by up to 40% in the presence of exogenous noradrenaline (1 μmol 1 −1 ). The inhibition by noradrenaline of depolarization‐evoked overflow was blocked by the α 1 /α 2 ‐adrenoceptor antagonist, phentolamine. Phentolamine alone did not increase K + ‐evoked 3 H overflow. 3 The α 2 ‐adrenoceptor antagonist, yohimbine, produced a concentration‐dependent block of the inhibition by noradrenaline of K + ‐evoked overflow, while the a 1 ‐adrenoceptor antagonist, prazosin, was without effect at concentrations up to 0.1 μmol 1 −1 . 4 The β‐adrenoceptor antagonist, propranolol, neither reduced K + ‐evoked overflow nor increased the degree of inhibition caused by the addition of 1 μmol 1 −1 noradrenaline. 5 The α 2 ‐adrenoceptor agonist, clonidine (1 μmol 1 −1 ) was less effective than noradrenaline at inhibiting K + ‐evoked overflow, while the α 1 ‐adrenoceptor agonist, phenylephrine (1 μmol 1 −1 ) had no significant effect. 6 The L‐channel calcium blocker, nicardipine (1 μmol 1 −1 ) significantly inhibited 3 H overflow evoked by K + . In the presence of L‐channel block, however, noradrenaline still inhibited residual evoked overflow. 7 In the presence or absence of nicardipine, pertussis toxin pretreatment (1 nmol 1 −1 ) reduced, but did not prevent, the effect of noradrenaline (1 μmol 1 −1 ). Pertussis toxin alone caused a significant enhancement of K + ‐evoked 3 H overflow. 8 The data indicate that on postganglionic neurones of cultured rat sympathetic ganglia there are α 2 ‐adrenoceptors that modulate neurotransmitter release, but no functional β‐adrenoceptors that mediate an enhancement of transmitter release. The data suggest further that in this preparation the mechanism of α 2 ‐adrenoceptor modulation may involve pertussis toxin sensitive and insensitive G‐proteins and effects on calcium channels other than L‐type.