Role of auto‐inhibitory feed‐back in cardiac sympathetic transmission assessed by simultaneous measurements of changes in 3H‐efflux and atrial rate in guinea‐pig atrium

• Published in: British journal of pharmacology 1984-01, Vol.81 (1), p.201-214
• Main Authors: Angus, J.A., Bobik, A., Jackman, G.P., Kopin, I.J., Korner, P.I.
• Format: Article
• Language: English
• Subjects: Animals; Desipramine - pharmacology; Dopamine - metabolism; Electric Stimulation; Feedback; Female; Guinea Pigs; Heart - innervation; Heart Rate - drug effects; In Vitro Techniques; Male; Methoxyhydroxyphenylglycol - analogs & derivatives; Methoxyhydroxyphenylglycol - metabolism; Myocardium - metabolism; Norepinephrine - metabolism; Phentolamine - pharmacology; Sympathetic Nervous System - drug effects
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1984.tb10762.x

1 Guinea‐pig right atria were labelled with [3H]‐noradrenaline or [3H]‐dopamine before superfusion in a flow‐cell. Choice of label did not significantly alter either the relationship between 3H‐efflux and number of electrical field pulses or the inhomogeneity of labelling. 2 The relationship between 3H‐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 3H‐efflux‐frequency relationship (Story, McCulloch, Rand & Standford‐Starr, 1981). 3 Phentolamine (1 μM) did not alter the 3H‐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 μm), rate and 3H‐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 3H‐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 α2‐adrenoceptors. Stimulation sufficient to induce a near‐maximal response or the presence of neuronal uptake inhibition are necessary to evoke auto‐inhibitory feed‐back.