LARGE DENSE-CORE VESICLES IN RAT ADRENAL AFTER RESERPINE - LEVELS OF MESSENGER-RNAS OF SOLUBLE AND MEMBRANE-BOUND CONSTITUENTS IN CHROMAFFIN AND GANGLION-CELLS INDICATE A BIOSYNTHESIS OF VESICLES WITH HIGHER SECRETORY QUANTA

Rats were injected with a large dose of reserpine known to stimulate t he adrenal medulla. Various times after drug treatment the mRNA levels of several constituents of large dense-core vesicles were determined by northern blot analysis and in situ hybridization. The latter method allowed detection of changes in mRNA levels not only in chromaffin ce lls, but also in the ganglion cells found in adrenal medulla. Levels o f the mRNAs of secretory components of large dense-core vesicles (chro mogranins A and B, secretogranin II, VGF, and neuropeptide Y) increase d in chromaffin cells by 215-857% after 1-3 days of drug treatment. Fo r partly membrane-bound components (dopamine beta-hydroxylase, prohorm one convertase 2, carboxypeptidase H, and peptidylglycine alpha-amidat ing monooxygenase) the changes ranged from 182 to 315%, whereas for gl ycoprotein III and for intrinsic membrane proteins (cytochrome b(561) and vesicle monoamine transporter 2) no change occurred. In ganglion c ells the mRNAs that could be detected for VGF, neuropeptide Y, secreto granin II, carboxypeptidase H, and vesicle monoamine transporter 1 sho wed an analogous pattern of change, with significant increases for the secretory proteins and no change for the membrane components. From th ese and previous results we suggest the following concept: Long-lastin g stimulation of chromaffin cells or neurons does not induce the biosy nthesis of a larger number of vesicles but rather leads to the formati on of vesicles containing higher secretory quanta of chromogranins and neuropeptides.