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Role of auto‐inhibitory feed‐back in cardiac sympathetic transmission assessed by simultaneous measurements of changes in 3 H‐efflux and atrial rate in guinea‐pig atrium
Author(s) -
Angus J.A.,
Bobik A.,
Jackman G.P.,
Kopin I.J.,
Korner P.I.
Publication year - 1984
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.1476-5381.1984.tb10762.x
Subject(s) - phentolamine , medicine , endocrinology , stimulation , inhibitory postsynaptic potential , atrium (architecture) , efflux , guinea pig , neurotransmission , desipramine , reserpine , chemistry , biology , receptor , biochemistry , antidepressant , hippocampus , atrial fibrillation
1 Guinea‐pig right atria were labelled with [ 3 H]‐noradrenaline or [ 3 H]‐dopamine before superfusion in a flow‐cell. Choice of label did not significantly alter either the relationship between 3 H‐efflux and number of electrical field pulses or the inhomogeneity of labelling. 2 The relationship between 3 H‐efflux and frequency of 4 field pulses (0.125–2 Hz) was hyperbolic and similar to the tachycardia‐frequency relationship measured simultaneously. No evidence was found for a U shaped 3 H‐efflux‐frequency relationship (Story, McCulloch, Rand & Standford‐Starr, 1981). 3 Phentolamine (1 μ M ) did not alter the 3 H‐efflux or atrial rate responses to 4 field pulses at stimulus levels that gave 50–60% of the maximum rate response. 4 In the presence of neuronal uptake inhibition (desipramine, DMI 0.1 μ m ), rate and 3 H‐efflux responses to 4 field pulses were enhanced at all frequencies and were further increased by phentolamine. 5 In the absence of DMI, prolonged trains of field pulses (8 and 12 pulses) at low frequency (0.25 Hz) were not sufficient to activate auto‐inhibitory feed‐back. At 2 Hz phentolamine enhanced both 3 H‐efflux and rate responses at 12 field pulses. 6 We conclude that in guinea‐pig right atrium auto‐inhibitory feed‐back plays little role in the modulation of transmitter release at levels of stimulation that cause 50–60% of maximum tissue response. This is because neuronal uptake normally prevents synaptic concentrations of noradrenaline from activating prejunctional α 2 ‐adrenoceptors. Stimulation sufficient to induce a near‐maximal response or the presence of neuronal uptake inhibition are necessary to evoke auto‐inhibitory feed‐back.