Chromaffin granules

Chromaffin granules, platelet dense core vesicles, and synaptic vesicles accumulate ATP. ATP uptake has been demonstrated using chromaffin granules and synaptic vesicles and the process appears to depend on A(.lh+. It has generally been assumed that ATP is costored only with monoamines and acetylcholine, as an anion to balance to cationic charge of those transmitters. However, the extent of ATP storage and release by different neuronal populations remains unknown, and the proteins responsible for ATP uptake by secretory vesicles have not been identified. 

Proteoglycans are also found in intracellular locations such as the nucleus their function in this organelle has not been elucidated. They are present in some storage or secretory granules, such as the chromaffin granules of the adrenal medulla. It has been posm-lated that they play a role in release of the contents of such granules. The various functions of GAGs are summarized in Table 48-8. 

Winkler, H (1993) The adrenal chromaffin granule a model for larger dense core vesicles of endocrine and nervous tissue. J. Anat. 183 237-252. 

Much of the early work on these transporters was carried out on the chromaffin granules of the bovine adrenal medulla. These studies revealed the transporter to be a polypeptide of 80kDa. However, two VMATs have now been characterised and these are the products of different genes. Evidence suggests that both have 12... 

Fig. 7.5. A schematic indication of some of the different membrane separated compartments in an advanced cell. PEROX is a peroxisome MITOCHLORO is either a mitochondrion or a chloroplast CHROMO is a vesicle of, say, the chromaffin granule ENDO is a reticulum, e.g. the endoplasmic reticulum. Other compartments are lysosomes, vacuoles, calcisomes and so on. Localised metal concentrations are shown. The figure is of a transverse section. To appreciate a cell fully it is necessary to have serial plane sections in parallel along the. "-direction.

Ordinarily, low concentrations of catecholamines are free in the cytosol, where they may be metabolized by enzymes including monoamine oxidase (MAO). Thus, conversion of tyrosine to l-DOPA and l-DOPA to dopamine occurs in the cytosol dopamine then is taken up into the storage vesicles. In norepinephrine-containing neurons, the final P-hydroxylation occurs within the vesicles. In the adrenal gland, norepinephrine is N-methylated by PNMT in the cytoplasm. Epinephrine is then transported back into chromaffin granules for storage. 

Moriyama, Y., and Nelson, N., 1988, Purification and properties of a vanadate- and N-ethylmaleimide- sensitive ATPase from chromaffin granule membranes. J. Biol. Chem., 263 8521-8527. 

Zachowski, A., Henry, J.P. and Devaux, P.F., 1989, Control of transmembrane hpid asymmetry in chromaffin granules by an ATP-dependent protein. Nature, 340 75-76... 

R.G. Johnson, S.E. Carty, S. Hayflick, A. Scarpa, Mechanisms of accumulation of tyramine, metaraminol, and isoproterenol in isolated chromaffin granules and ghosts, Biochem. Phamacol. 31 (1982) 815-823. 

The principal mechanism for the deactivation of released catecholamines is, however, not enzymatic destmction but reuptake into the nerve ending. The presynaptic membrane contains an amine pump—a saturable, high-affinity, Na" -dependent active-transport system that requires energy for its function. The recycled neurotransmitter is capable of being released again, as experiments with radiolabelled [ H]NE have shown, and can be incorporated into chromaffin granules as well. Many drugs interfere with neurotransmitter reuptake and metabolism, as discussed in subsequent sections. 

A different example involves the proteins of the interior of the chromaffin granule—the chromogranin A proteins.57 Physical measurements using the ultra centrifuge57 showed that these proteins were not globular, and detailed nmr studies58 indicate that the proteins are largely in the random coil form as the nmr spectrum is relatively sharp and the spectrum is the sum of the spectra of the component amino acids. This protein has been examined in the vesicles of the adrenal medulla in vivo... 

Creutz, C. E., Pazoles, C. J. and H.B. Pollard, 1978, Identification and purification of an adrenal medullary protein (synexin) that causes calcium-dependent aggregation of isolated chromaffin granules. J. Biol. Chem. 253, 2858-2866. 

AThe subunit has been confirmed for the insect (Merzendorfer et al, 1999) and chromaffin granule enzyme (Ludwig et al, 1998) and has recently been found in the yeast enzyme (Sambade and Kane, 2004). The subunit compositions of the F-ATPase from the bacterium Escherichia coli, the vacuolar ATPase from yeast and bovine brain clathrin-coated vesicles, and the A-ATPase from the Archaeon Thermoplasma acidophilum are listed. Molecular masses are calculated from the amino acid sequence where available. 

Ludwig,J., Kerscher, S., Brandt, U., Pfeiffer, K., Gedawi, F., Apps, D. K., and Schagger, H. (1998). Identification and characterization of a novel 9.2-kDa membrane sector-associated protein of vacuolar proton ATPase from chromaffin granules. J. Biol. Chem. 273, 10939-10947. 

Reserpine blocks the ability of aminergic transmitter vesicles to take up and store biogenic amines, probably by interfering with an uptake mechanism that depends on Mg2+ and ATP (Figure 6-4, carrier E). This effect occurs throughout the body, resulting in depletion of norepinephrine, dopamine, and serotonin in both central and peripheral neurons. Chromaffin granules of the adrenal... 

Darchen F, Scherman D, Henry JP (1989) Reserpine binding to chromaffin granules suggests the existence of two conformations of the monoamine transporter. Biochemistry 28 1692-1697. 

Johnson RG, Jr. (1988b) Accumulation of biological amines into chromaffin granules a model for hormone and neurotransmitter transport. Physiol Rev 68 232-307. 

Knoth J, Zallakian M, Njus D (1981) Stoichiometry of H+-linked dopamine transport in chromaffin granule ghosts. Biochemistry 20 6625-6629. 

Peter D, Jimenez J, Liu Y, Kim J, Edwards RH (1994) The chromaffin granule and synaptic vesicle amine transporters differ in substrate recognition and sensitivity to inhibitors. J Biol Chem 269 7231-7237. 

Rudnick G, Steiner-Mordoch SS, Fishkes H, Stern-Bach Y, Schuldiner S (1990) Energetics of reserpine binding and occlusion by the chromaffin granule biogenic amine transporter. Biochemistry 29 603-608. 

Sagne C, Isambert MF, Vandekerckhove J, Henry JP, Gasnier B (1997) The photoactivatable inhibitor 7-azido-8-iodoketanserin labels the N terminus of the vesicular monoamine transporter from bovine chromaffin granules. Biochemistry 36 3345-3352. 

Sulzer D, Rayport S (1990) Amphetamine and other psychostimulants reduce pH gradients in midbrain dopaminergic neurons and chromaffin granules a mechanism of action. Neuron 5 797-808. 

Weaver JA, Deupree JD (1982) Conditions required for reserpine binding to the catecholamine transporter on chromaffin granule ghosts. Eur J Pharmacol 80 437 438. 

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