Endocrine secretory granules and neuronal synaptic vesicles have three integral membrane proteins in common.

Abstract

Abstract. In response to an external stimulus, neuronal cells release neurotransmitters from small synaptic vesicles and endocrine cells release secretory proteins from large dense core granules. Despite these differences, endocrine cells express three proteins known to be components of synaptic vesicle membranes. To determine if all three proteins, p38, p65, and SV2, are present in endocrine dense core granule membranes, monoclonal antibodies bound to beads were used to immunoisolate organelles containing the synaptic vesicle antigens. [3H]norepinephrine was used to label both chromaffin granules purified from the bovine adrenal medulla and rat pheochromocytoma (PC12) cells. Up to 80% of the vesicular [3H]norepinephrine was immunoisolated from both labeled purified bovine chromaflin granules and PC12 postnuclear supernatants. In PC12 cells transfected with DNA encoding human growth hormone, the hormone was packaged and released with norepinephrine.

Quantification of p38/synaptophysin in highly purified adrenal medullary chromaffin vesicles

“…This observation is, however, not at variance with the data presented here since the lower density of p38 per mg of membrane protein (about 20 times) in chromaffin vesicles would reduce the number of gold particles per cross-section of vesicle to background levels. The present results are suited to explain the recent finding that chromaffin vesicles can be bound to p38 antibody-coated beads [8]. Clearly, 20 molecules of p38 per vesicle would be sufficient to bind chromaffin vesicles as well as clear (synaptic) vesicles to such beads.…”

“…Recently it has been reported [8] that p38/synaptophysin also occurs in hormone containing large dense core vesicles. This would imply that p38/synaptophysin could fulfill similar functions…”

A high ratio of chromogranin A to synaptin/synaptophysin is a common feature of brains in Alzheimer and Pick disease

“…Synaptin/synaptophysin is a protein found in high concentrations in synaptic vesicles [5][6][7], and in lower concentration in large dense core vesicles and in endocrine vesicles like chromaffin granules [5,8,9]. Its consistent low levels in Alzheimer's (which is in agreement with immunohistochemical data [19,20]) and Pick's brains can simply be an expression of neuronal and synaptic loss occurring in these diseases, but a specific loss of synaptic vesicles should also be considered.…”

“…Synaptin/synaptophysin [4] is found in high concentrations in synaptic vesicles [5][6][7], but also in large dense core vesicles and endocrine vesicles [5,8,9]. Recently it has been reported that a monoclonal antibody against chromogranin A recognizes the characteristic plaques of Alzheimer's disease [10] indicating the presence of chromogranin immunoreactive material in these lesions.…”

Vasoactive intestinal polypeptide (VIP) as a cholinergic co-transmitter: Some recent results

“…A neat explanation of the inverse frequency dependence of acetylcholine and VIP would be to suppose that the exocytosis of the VIP-rich vesicles occurs at a different site in the terminal (where L-type Ca*+-channels are concentrated) from that at which acetylcholine-rich synaptic vesicles undergo exocytosis and where N-type channels may be concentrated (Fig 3). It has been suggested (Geffen and Livett, 1971;Lowe et al, 1988) that in the adrenergic system the membranes of dense-cored vesicles, which contain the small-molecular-mass transmitter noradrenaline as well as neuropeptides are retrieved to form small, electron-lucent vesicles which are competent to take up and release noradrenaline and recycle in the terminal. It may be that this precursor-product relationship also exists, at least in cholinergic neurones of the guinea-pig myenteric plexus, between acetylcholine-containing, VIPrich storage particles and acetylcholine-rich synaptic vesicles, which, as we have seen, are able to recycle and thus to sustain acetylcholine release independently of axons1 transport.…”