Depletion and Replacement of the Adrenaline and Noradrenaline Contents of the Rat Adrenal Gland, Following Treatment With Reserpine

Abstract

The effect of reserpine on the adrenaline and noradrenaline contents of rat adrenal glands has been studied. Given subcutaneously to male albino Wistar rats in 3 daily doses of 1 mg/kg, it caused, 24 hr after the final dose, a similar percentage loss of adrenaline and noradrenaline of approximately 50%. Subsequently the adrenaline content slowly increased, until at 14 days from the begining of the experiment there was no significant difference between the reserpine-treated and the control glands. In contrast, the recovery of the noradrenaline content was rapid, exceeding the control value at 7 days by approximately 250%. This increased content of noradrenaline declined to the normal level by 21 days. The total amine content returned to normal by 7 days and remained at this level subsequently. The effect of re-depleting the glands of their amine content was investigated. It was found that re-depletion at 7 days caused a preferential release of noradrenaline, followed at 14 days by a peak of noradrenaline at least as high as that obtained following the initial depletion only. Re-depletion at 21 days caused an effect similar to that obtained initially. Denervation of the left adrenal gland did not alter the degree of depletion caused by reserpine, nor did it alter the subsequent replacement of the amines as compared with that in the innervated right gland.In 1956 Holzbauer & Vogt showed that reserpine caused a loss of adrenaline and noradrenaline from the adrenal gland of the cat. Carlsson & Hillarp (1956) demonstrated a similar effect in the rabbit adrenal gland, and Parratt & West (1957) noted that the adrenal gland of the rat was markedly depleted by doses of 10 mg/kg of reserpine. Taketomo, Shore, Tomich, Kuntzman & Brodie (1957) found that, following depletion of the rabbit adrenal gland, 5 to 7 days were necessary for the amine stores to be replenished and that the depletion could be prevented by section of the spinal cord at the level of the first thoracic segment. Kroneberg & Schumann (1957a) also demonstrated that recovery was slow and that cutting the splanchnic nerves one week previously only partially protected the glands from depletion. Muscholl & Vogt (1958) found that 14 days were necessary for replacement of the catechol amine content of the rabbit adrenal medulla following depletion by a single intravenous dose of 1.6 mg/kg of reserpine. They also showed that the relative proportions of adrenaline and noradrenaline were normal even in glands still partially depleted at 8 to 9 days.

Urinary Excretion of Catechol Amines in the Rat After Their Liberation by Reserpine or Dexamphetamine

“…The adrenaline content of the adrenal gland is only moderately depleted by the doses of reserpine here employed (Callingham & Mann, 1962); therefore there is no functional inactivation of the adrenal medulla. Indeed, reserpine causes an increased adrenaline excretion which is reduced by the administration of mecamylamine.…”

The Pharmacology of Rauwolfia Alkaloids

“…It was reported that noradrenaline is selectively depleted from adrenal glands of mouse (ERANKO and Hopsu, 1958) and cat (STJARNE and SCHAPIRO, 1959) but this does not occur in rats (COUPLAND, 1958;CALLINGHAM and MANN, 1962). The rate of depletion of adrenal stores is slower than that of amine stores in brain or other peripheral tissues (CALLINGHAM and MANN, 1962), and higher doses of reserpine are required (CARLSSON et aI., 1957 a;LEE, 1967). The relative insensitivity of the adrenal medulla to depletion arises from the slower turn-over rate of medullary amines than of amines in other tissues.…”

“…During repletion, there is a considerable overshoot of the noradrenaline content (250% of control) after 7 days followed by a return to the control value in 21 days (CALLINGHAM and MANN, 1962). The ability of adrenal storage granules to accumulate labelled catecholamine returns after reserpine treatment well before the normal levels are restored (LUNDBORG, 1963).…”

“…However, in the rat, depletion of adrenal catecholamines by reserpine is not affected by splanchnic nerve section (MIRKIN, 1958;CALLINGHAM and MANN, 1962) or by spinal section at C6 (KRONEBERG and SCHUMANN, 1957b). It was suggested that reserpine may act centrally in small doses to cause depletion of the adrenal catecholamines, but large doses have a more direct peripheral action which overshadows any central effect; most studies in the rat have been concerned with the latter effect (CALLINGHAM and MANN, 1962).…”

“…It was suggested that reserpine may act centrally in small doses to cause depletion of the adrenal catecholamines, but large doses have a more direct peripheral action which overshadows any central effect; most studies in the rat have been concerned with the latter effect (CALLINGHAM and MANN, 1962).…”