Granules Of Adrenal Medulla Research Articles

Differential Responses of Genes for Neurosecretory Granules in the Rat Adrenal Medulla to Acute and Repeated Stress

With acute stress, release of adrenomedullary catecholamines is important for handling the emergency situation. However, when chronic or repeated, stress leads to development or worsening of wide range of diseases. To clarify the mechanism, we studied changes in components of neurosecretory granules in adrenal medulla of male Sprague Dawley rats exposed to immobilization stress for 2 h once (1xIMO) or for 6 days (6xIMO). While vesicular monoamine transporter 1 (VMAT1) was expressed in all chromaffin cells, VMAT2, which has greater affinity for catecholamines, and higher turnover number than VMAT1, was expressed only in the NE‐cells under basal conditions. 1xIMO elevated VMAT2 mRNA, and after 6xIMO, this was reflected in nearly 3‐fold rise in VMAT2 protein, and expression in many Epi‐synthesizing cells. With 6xIMO, not only was VMAT2 mRNA still elevated, but chromogranin A (CgA) and chromogranin B (CgB) mRNAs were also increased 2–3 fold. The elevation of CgA, CgB and VMAT2 are each expected to increase the quantal size. This can facilitate more efficient use of the well characterized heightened catecholamine levels. To investigate a possible role of the HPA axis in induction of VMAT2, PC12 cells were treated with dexamethasone, which elevated VMAT2 mRNA expression. In contrast, the rise in Egr1 and P‐CREB may mediate the induction of CgA and CgB with repeated IMO stress.American Heart Association 10GRNT4420001

Stress triggered changes in expression of genes for neurosecretory granules in adrenal medulla.

With acute stress, the release of adrenomedullary catecholamines is important for handling the emergency situation. However, when chronic or repeated, stress alters the allostatic load and leads to a hyperadrenergic state, resulting in the development or worsening of a wide range of diseases. To help elucidate the mechanism, we examined the effects of single and repeated immobilization stress on gene expression of components of neurosecretory vesicles in the adrenal medulla. Male Sprague-Dawley rats were exposed to immobilization stress once for 2h (1× IMO) or daily for six consecutive days (6× IMO). Compared to unstressed controls, 1× IMO elevated gene expression of vesicular monoamine transporter 2 (VMAT2). In response to 6× IMO, not only was VMAT2 mRNA still elevated, but chromogranin A (CgA) and chromogranin B (CgB) mRNAs were also increased two to three-fold above basal levels. To investigate the possible role of the hypothalamic-pituitary-adrenal axis in the induction of VMAT2, PC12 cells were treated with the synthetic glucocorticoid dexamethasone, which was found to elevate VMAT2 mRNA expression. The findings suggest that following repeated stress, elevations of various components of neurosecretory vesicles in the adrenal can facilitate more efficient utilization of the well-characterized heightened catecholamine levels.

Fluorescence properties of catecholamines in isolated storage organelles of adrenal medulla

Abstract THe quantum yield, the life time and the degree of polarization of the fluorescence of intact chromaffin granules isolated from bovine adrenal medulla were compared to those of catecholamines solutions and catecholamine/ATP mixtures. Rising concentrations of catecholamines in aqueous solutions exhibited increasing quenching and decreasing life times indicating that the quenching was collision induced. Similar effects occurred in mixtures of catecholamines with ATP and Ca 2+ showing that the nucleotide did not remarkedly hinder the mobility of the catechol group. In suspensions of whole granules stron quenching and shortening of life time was observed compared with solutions of disrupted granules. Fluorescence yield and life time were decreased by about the same factor suggesting that storage of the amines was not correlated with a major immobilization of the catechol group. The degree of polarization of intact granules was higher than that of solutions of catecholamines alone, but similar to catecholamine/ATP mixtures with concentrations corresponding to those found in the granules. This indicates an interaction of catecholamines with ATP in the granules. The results are in agreement with a storage model for catecholamines in the chromaffin granules of adrenal medulla in which catecholamines are bound to ATP, but in a non-rigid way.

Immunohistochemical demonstration of a membrane protein of chromaffin granules in adrenal medulla and symphathetic nerve.

A rabbit antiserum was obtained against a protein isolated from membranes of bovine chromaffin granules. Immunohistochemical evidence indicates that this protein is present in the adrenal medullae of several species and in bovine sympathetic nerve.

Structural changes in the catecholamine containing granules of adrenal medulla

Turbidity changes in the catecholamine containing granules of adrenal medulla were caused by Ca 2+, ATP-Mg 2+, reserpine or tyramine which are known to stimulate the release of catecholamine from the granules. However, the turbidity change caused by tyramine was slight. It was suggested therefore, that Ca 2+, ATP-Mg 2+ or reserpine might cause some structural changes in the catecholamine containing granules, resulting in a release of catecholamine from the granules. It is uncertain whether the slight changes in the structural state of the granules caused by tyramine contribute to the release of catecholamine from the granules stimulated by tyramine.

Stimulatory effect of adenosine triphosphate and magensium on the release of catecholamines from adrenal medullary granules.

It is well known that catecholamine is stored within specific granules in various tissues and when it is released from these granules it displays its physiological effects. Therefore, the mechanisms of storage and release of catecholamine have recently become a topic of interest. It was reported by Kirshner (1) and Carlsson et al. (2) that the uptake of 14C-catecholamine into the granules of the adrenal medulla was stimulated by ATP and Mg2+. Euler and Lishajko also showed ATP-Mg2+ dependent uptake of catecholarnine by the granules of adrenergic nerves (3, 4). The effect of ATP and Mg2+ on the uptake and release of catecholamine in the granules of adrenal medulla was also studied in this laboratory. It was found that on the addition of ATP and Mg2+, there was only slight or no inhibition of the release of catecholamine from the granules when they were incubated in sucrose solution, while when they were incubated in saline solution catecholamine release was greatly stimulated. This report gives further details of the stimulatory effect of ATP and Mg2+ on the release of catecholamine from the granules of adrenal medulla. A preliminary report of this work has been published (5, 6).

Adenosinephosphates and inorganic phosphate in the adrenaline and noradrenaline containing granules of the adrenal medulla.

Summary.1. The catechol amine containing granules of the cow adrenal medulla have been isolated as a fraction of high purity by density gradient centrifugation. They have a very high content of amines (34.3 μmoles/mg protein‐N) and ATP (7.6 μmoles). Smaller amounts of ADP (0.89 μmoles), AMP (0.27 μmoles) and inorganic phosphate (1.45 μmoles) are also present. The adenosinephosphates represent at least 95 per cent of the acid soluble organic phosphates in the granules.2. The molar ratio amines: ATP is 4.5: 1 or 3.9: 1, if the ADP and AMP in the granules are assumed to be split products from ATP. The sum of adenosinephosphates and inorganic phosphate represents an amount of acid equivalent to the catechol amines. This suggests that the amines are stored in intimate relation to the phosphates.3. The osmotic properties of the granules and the amine content found in them make it necessary to assume that the amines are incorporated, together with the adenosinephosphates, in a complex molecular structure which prevents them from forming free ions or molecules in the intragranular water. The presence of large amounts of water soluble proteins (77—78 per cent of the total proteins) within the granules suggests that these proteins are a component in the postulated structure.