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.
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. 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). Phentolamine (1 microM) 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. In the presence of neuronal uptake inhibition (desipramine, DMI 0.1 microM), rate and 3H-efflux responses to 4 field pulses were enhanced at all frequencies and were further increased by phentolamine. 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. 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 alpha 2-adrenoceptors. Stimulation sufficient to induce a near-maximal response or the presence of neuronal uptake inhibition are necessary to evoke autoinhibitory feed-back.
D000818:Animals; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D005246:Feedback; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*
D008734:Methoxyhydroxyphenylglycol; D003891:Desipramine; C010117:3,4-dihydroxyphenylglycol; D004298:Dopamine; D009638:Norepinephrine; D010646:Phentolamine