Effect of Tyramine on Isolated Guinea‐pig Atria in Relation to Their Noradrenaline Stores

Abstract

The relation between the noradrenaline content of isolated guinea-pig atria and the rate-increasing action of tyramine was studied by the use of pretreatment with reserpine as a pharmacological tool for graded depletion of the noradrenaline stores. Reserpine was more potent in depleting the stores than in reducing the biological response to tyramine; 50% depletion had little effect on the response to tyramine; 50% reduction of the response to tyramine occurred when the noradrenaline content fell to about 10% of normal. Depletion of the store's of guinea-pig atria did not result in supersensitivity to noradrenaline. Exposure of heavily pretreated atria to 3 x 106 noradrenaline for 10 min (followed by repeated washing for 45 min) restored the response to tyramine to 70% of normal; it failed, however, to restore the noradrenaline content to the level expected from the experiments with reserpine alone. Restoration of the response to tyramine was accompanied by a small but significant increase in the noradrenaline content of the atria; a change in sensitivity to added noradrenaline did not occur. The results are consistent with the view that (a) the noradrenaline stores consist of two compartments the smaller of which is important for the action of tyramine, that (b) this smaller compartment can be at least partially refilled by exposure of the atria to noradrenaline, and that (c) there is no direct relationship between the noradrenaline content and the-sensitivity to noradrenaline in guinea-pig atria.It is well known that reserpine depletes the noradrenaline stores of peripheral organs (Carlsson, Rosengren, Bertler & Nilsson, 1957;Paasonen & Krayer, 1958;Burn & Rand, 1959) and abolishes the response of such tissues to tyramine and to stimulation of adrenergic nerves (Carlsson et al., 1957;Burn & Rand, 1958;Trendelenburg & Gravenstein, 1958). Tyramine is therefore generally assumed to exert its sympathomimetic effects through the liberation of noradrenaline from peripheral noradrenaline stores. Although various studies deal with the effects of pretreatment with graded doses of reserpine, they have been restricted either to the observation of -biological responses believed to be mediated through the liberation of noradrenaline (Fleming & Trendelenburg, 1961 ;Trendelenburg, 1961;Liebman, 1961;Waud, 1961 ;Liebman, Muskus & Waud, 1962) or to the determination of catechol amine content (Carlsson et al., 1957). Since no attempt has yet been made to correlate these two phenomena quantitatively, it is not known how TYRAMINE AND NORADRENALINE STORES much the noradrenaline stores must be depleted to reduce the sympathomimetic action of tyramine.Although it is well established that noradrenaline restores the response of reserpine-pretreated preparations to tyramine (Burn & Rand, 1958, 1960 and to nerve stimulation (Burn & Rand, 1958;Gillespie & Mackenna, 1961), restoration of the noradrenaline stores has been observed by some authors (Pennefather & Rand, 1960) but not by others (Muscholl, 1960).It was thus of interest to study ...

Recovering Effect of Acetylcholine on the Depressed Atrial Transmembrane Potential of the Reserpinized Rabbit by the Adrenolytics

“…No linear correlation between the content of atrial noradrenaline and the sensitivity of the atria to exogenous noradrenaline in guinea pig was shown by Crout et al (16). The hypersensitivity of the pressor response of the reserpinized cat to catecholamine was demonstrated by Burn et al (20).…”

“…About thirty reserpinized rabbits were used in the experiments. The animals received 0.5 mg/kg of reserpine intraperi toneally at 48 and 24 hours before the extirpation of heart, of which doses were enough to deprive the heart catecholamine almost completely (15,16). The recordings of the transmembrane potential were made at least one hour after the fixation of the prepara tion on the cork plate in the modified Tyrode solution, maintained at 30°C and saturated with 95% 02 and 5% CO2.…”

Cardiac Noradrenaline Stores

“…Muscholl (1960) and Furchgott & Kirpekar (1961) noted only the effect of noradrenaline repletion in rat and guinea-pig atria before treatment of the animals with reserpine, but could detect no increase in noradrenaline content. On the other hand, Crout et al (1962) found an increase in noradrenaline after repletion of guinea-pig isolated atria, although it was less than 2% of the normal noradrenaline content and much smaller than the increase we noted for the dog.…”

“…During our work, Gaffney (1961) and Krayer, Alper & Paasonen (1962) have reported the acute effects of guanethidine on the dog isolated heart, and Krayer et al (1962), Crout, Muskus & Trendelenburg (1962) and Fawaz (1963) have reviewed the subject.…”

ASPECTS OF THE BIOGENIC AMINE‐DEPLETING ACTIVITY OF ETHYL 3‐ACETAMIDO‐4H‐PYRROLO‐[3,4‐c]ISOXAZOLE‐5(6H)‐CARBOXYLATE IN THE RAT

“…Thus an early physiological effect, such as a decrease in blood pressure, might be produced in the absence of a large reduction in tissue noradrenaline concentration. Furthermore, only a relatively small amount of the noradrenaline present in tissues seems normally to be released after physiological stimulation of the adrenergic nerves (Crout, Muskus & Trendelenburg, 1962;von Euler, 1963;Kernell & Sedvall, 1964) and this might be the noradrenaline involved in the initial effect of CL-62375. Also, the bound noradrenaline is stored in a physiologically inert, chemically unchanged form (Potter & Axelrod, 1963).…”