Interaction between presynaptic facilitatory angiotensin II receptors and inhibitory muscarinic cholinoceptors on3H-noradrenaline release in the rabbit heart |
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Authors: | Jesús A García-Sevilla Margarita L Dubocovich Salomon Z Langer |
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Institution: | (1) Departamento de Farmacología y Terapéntica, Facultad de Medicina, Universidad del País Vasco, Leioa, Vizcaya, Spain;(2) Present address: Department of Pharmacology, Northwestern University Medical School, 303 East Chicago Avenue, 60611 Chicago, Illinois, USA;(3) Department of Biology, Synthélabo (L. E. R. S.), F-75013 Paris, France |
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Abstract: | Summary The existence of a functional interaction between presynaptic receptors modulating the release of noradrenaline was studied in the rabbit heart. Isolated right atria were prelabelled with3H-noradrenaline and the overflow of tritium was induced by field stimulation (2 Hz, 0.1 ms duration, supramaximal voltage for a total of 180 pulses). In atria superfused with Krebs' solution containing 10 mol/l cocaine and 30 mol/l corticosterone, angiotensin II (10 nmol/l) increased the stimulation-evoked overflow of3H-transmitter by 2.8-fold. The addition of atropine (0.3 mol/l) to the perfusion medium, either in the presence or in the absence of uptake inhibitors, further enhanced the facilitatory effect of angiotension II (3H-transmitter release increased by 3.5-fold). Exposure to 1 mol/l carbachol decreased by 65% the stimulation-evoked release of3H-transmitter while the facilitatory effect of angiotensin II determined in the presence of the muscarinic cholinoceptor agonist was enhanced (3H-transmitter release increased by 6.6-fold). Conversely, during sustained activation of presynaptic angiotensin receptors producing a 2.5-fold increase in the release of3H-transmitter, the inhibitory effect of carbachol remained unchanged. These results suggest a functional interaction between presynaptic inhibitory muscarinic cholinoceptors and the presynaptic facilitatory angiotensin receptor which modulate the release of noradrenaline from cardiac noradrenergic nerves. |
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Keywords: | Presynaptic angiotensin receptor Presynaptic muscarinic cholinoceptor 3H-Noradrenaline release Rabbit atria |
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