Facilitation of secretion of catecholamines from rat and guinea-pig adrenal glands in potassium-free medium or after ouabain.

1. The effect of K deprivation on catecholamine (CA) secretion induced by transmural stimulation of the isolated perfused adrenal glands of the rat was studied. 2. In the absence of external K, secretion of CA evoked by transmural stimulation was greatly (2- to 7-fold) facilitated. The facilitation was inversely related to the frequency of stimulation. The duration of CA secretion upon stimulation was prolonged significantly in K-free medium as compared to that in Krebs solution. 3. CA secretion evoked by acetylcholine (ACh) in K-free Krebs solution was increased by about 40%, with little change in the duration of secretion. 4. Chronic denervation of the adrenal gland practically abolished secretory response induced by transmural stimulation without affecting secretion of CA by ACh. Perfusion of the denervated adrenal gland with K-free solution enhanced ACh-induced CA secretion by about 40%, and a secretory response to transmural stimulation became evident. 5. Spontaneous secretion of CA was increased from a control value of about 2 ng/min to 56 ng/min 35 min after perfusion with K-free Krebs solution. During enhanced spontaneous secretion, electrical stimulation of the adrenal gland produced facilitation of secretion. 6. Spontaneous secretion of CA in K-free medium was only slightly reduced by lowering Ca to 0.25 mM, but that evoked by stimulation was markedly depressed. However, spontaneous and evoked secretion in K-free medium were totally blocked upon removal of Ca and addition of 5 mM-EGTA. 7. Re-introduction of 2.5 mM-Ca 6 min after stimulation of the adrenal gland in 0.25 mM-Ca, K-free solution produced a marked secretory response. 8. Lowering of Ca to 0.25 mM immediately after stimulation of the adrenal gland in K-free solution significantly reduced the amounts of CA secreted in the post-stimulation period. 9. Ouabain (0.14-1.4 mM) did not enhance secretion of CA in unstimulated preparations or after transmural stimulation of the rat adrenal gland. ACh-induced secretion was more than doubled by ouabain. 10. Not only was spontaneous secretion of CA from the guinea-pig adrenal gland enhanced by K deprivation or ouabain, but secretion evoked by transmural stimulation or by ACh was also facilitated in K-free medium by ouabain (0.7-7.0 microM). 11. Enhanced secretion of CA in unstimulated preparations or after transmural stimulation of the adrenal gland, in the absence of K, has been attributed to the excess release of ACh from splanchnic nerve terminals. The enhanced release of ACh has been attributed to the elevation of free cellular CA resulting from blockade of the Na pump. On the other hand, ouabain facilitates CA secretin in the rat and guinea-pig adrenal glands predominantly by its effect on the chromaffin cells.