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J Meldolesi

Publications and source records attributed to J Meldolesi.

At least 181 records · Page 10Linked to original sources
PubMed1984

alpha Latrotoxin of black widow spider venom binds to a specific receptor coupled to phosphoinositide breakdown in PC12 cells.

alpha Latrotoxin of black widow spider is known to bind with high affinity to surface sites of rat pheochromocytoma (PC12) cells, thereby causing depolarization, calcium influx and massive neurotransmitter release. We show here that the toxin causes the accumulation of inositol phosphates, the products of phosphoinositide breakdown. Inositol 1,4,5, trisphosphate was predominantly accumulated shortly after toxin application. Phosphoinositide breakdown appears to be a direct consequence of toxin binding because high K+ and ionophores (which induce depolarization, calcium influx and transmitter release by different mechanisms) were without such effect. Phosphoinositide breakdown is known as an event coupled to the activation of receptors of various hormones and transmitters. We suggest therefore that the alpha latrotoxin binding site is a receptor coupled across the membrane to the phosphoinositide hydrolysing system.

Adrenal Gland Neoplasms↗
PubMed1984

Alpha-latrotoxin and glycerotoxin differ in target specificity and in the mechanism of their neurotransmitter releasing action.

alpha-Latrotoxin, a high molecular weight protein (130,000) purified from the venom of the black widow spider, and a partially purified neurotoxin, glycerotoxin, prepared from extracts of the jaw glands of the polichaete annelid Glycera convoluta, were previously found to induce similar effects (stimulation of quantal acetylcholine release) at the frog neuromuscular junction. In the present study parallel experiments performed with these two toxins revealed that only glycerotoxin was able to release acetylcholine from Torpedo electric organ synaptosomes, while alpha-latrotoxin did not affect release in this system. In contrast, alpha-latrotoxin stimulated release of dopamine from PC12 cells (a cloned neurosecretory cell line), whereas glycerotoxin was almost inactive. In rat brain synaptosomes both toxins were active. Preincubation of synaptosomal membranes with glycerotoxin was without effect on the subsequent binding of alpha-latrotoxin. Glycerotoxin application induced depolarization of synaptosomal plasma membrane, massive Ca2+ influx, marked increase of the cytosolic Ca2+ concentration, and stimulation of catecholamine release. The latter effect occurred to the same extent when glycerotoxin was applied either in complete medium (containing both Ca2+ and Mg2+), Ca2+-free medium or divalent cation-free medium. Some of these effects of glycerotoxin in rat brain synaptosomes (depolarization, increased Ca2+ influx and increased cytosolic Ca2+ concentration) resemble effects previously reported for alpha-latrotoxin. However, the secretory response induced by the latter was reduced in Ca2+-free, and abolished in divalent cation-free media. The different target specificity and the lack of binding competition of the two toxins could be due to their ability to recognize different receptors whose distribution overlap only in part in the cellular systems we have studied. The differences in action, on the other hand, could depend on postreceptor events, possibly related to the transmembrane insertion of toxin molecules demonstrated by others in artificial lipid membranes.

Animals↗
PubMed1984

Free cytoplasmic Ca2+ and neurotransmitter release: studies on PC12 cells and synaptosomes exposed to alpha-latrotoxin.

The relationship between the free cytoplasmic Ca2+ concentration, [Ca2+]i, and neurotransmitter release was investigated in guinea pig brain synaptosomes and the neurosecretory cell line PC12. Release was induced by alpha-latrotoxin, which acts in both Ca2+ -containing and Ca2+ -free incubation media, or by the classical depolarizing agents high K+ and veratridine, which require extracellular Ca2+. Two complementary approaches were used to reveal changes of [Ca2+]i: (i) direct measurement by a fluorescent Ca2+ indicator (quin2) and (ii) study of the Ca2+ -dependent phosphorylation of a protein, synapsin I, located at the cytoplasmic surface of synaptic vesicles. Depolarizing agents, when applied in Ca2+ -containing medium, induced the [Ca2+]i to increase promptly 3- to 6-fold, drastically increased synapsin I phosphorylation, and caused stimulation of transmitter release. With alpha-latrotoxin, the [Ca2+]i increase was delayed and occurred at a slower rate, the increase of synapsin I phosphorylation was less drastic, and the release response was much more pronounced. In Ca2+ -free medium, depolarizing agents released no transmitter and had no effect on [Ca2+]i or synapsin I phosphorylation, whereas with alpha-latrotoxin these processes were dissociated: considerable stimulation of the release without apparent change of [Ca2+]i and synapsin I phosphorylation. We conclude that the relationship between average [Ca2+]i and transmitter release is not straightforward and, in particular, that the release evoked by alpha-latrotoxin in Ca2+ -free medium is mediated by a factor(s) other than bulk redistribution of Ca2+ from intracellular stores.

Aminoquinolines↗
PubMed1984

Specific localization of the alpha-latrotoxin receptor in the nerve terminal plasma membrane.

The receptor for alpha-latrotoxin, the major protein component of the black widow spider venom, was investigated by the use of the purified toxin and of polyclonal, monospecific anti-alpha-latrotoxin antibodies. Experiments on rat brain synaptosomes (where the existence of alpha-latrotoxin receptors was known from previous studies) demonstrated that the toxin-receptor complex is made stable by glutaraldehyde fixation. At saturation, each such complex was found to bind on the average five antitoxin antibody molecules. In frog cutaneous pectoris muscles, the existence of a finite number of high-affinity receptors was revealed by binding experiments with 125I-alpha-latrotoxin (Kd = 5 X 10(-10) M; bmax = 1.36 +/- 0.16 [SE] X 10(9) sites/mg tissue, dry weight). Nonpermeabilized muscles were first treated with alpha-latrotoxin, and then washed, fixed, dissociated into individual fibers, and treated with anti-alpha-latrotoxin antibodies and finally with rhodamine-conjugated sheep anti-rabbit antibodies. In these preparations, muscle fibers and unmyelinated preterminal nerve branches were consistently negative, whereas bright specific fluorescent images, indicative of concentrated alpha-latrotoxin binding sites, appeared in the junctional region. These images closely correspond in size, shape, and localization to endplates decorated by the acetylcholinesterase reaction. The presynaptic localization of the specific fluorescence found at frog neuromuscular junctions is supported by two sets of findings: (a) fluorescent endplate images were not seen in muscles that had been denervated; and (b) the distribution of fluorescence in many fibers treated with alpha-latrotoxin at room temperature was the one expected from swollen terminal branches. Swelling of terminals is a known morphological change induced by alpha-latrotoxin in this preparation. When muscles were treated with either proteolytic enzymes (trypsin, collagenase) or detergents (Triton X-100) before exposure to alpha-latrotoxin, the specific fluorescent endplate images failed to appear. Taken together these findings indicate that the alpha-latrotoxin receptor is an externally exposed protein highly concentrated in the nerve terminal plasma membrane. Its density (number per unit area) at the frog neuromuscular junction can be calculated to be approximately 2,400/micron2.

Animals↗
PubMed1984

Ca2+-dependent and -independent release of neurotransmitters from PC12 cells: a role for protein kinase C activation?

The intracellular mechanisms regulating the process of evoked neurotransmitter release were studied in the cloned neurosecretory cell line PC12. Various agents were employed that were known, from previous studies in other systems, to stimulate release in a manner either strictly dependent or independent of the concentration of extracellular Ca2+, [Ca2+]o. Three parameters were investigated in cells suspended in either Ca2+-containing or Ca2+-free Krebs-Ringer media: release of previously accumulated [3H]dopamine; average free cytoplasmic Ca2+ concentration, [Ca2+]i (measured by the quin2 technique); and cell ultrastructure, with special reference to the number and structure of secretion granules. The release induced by the ionophores transporting monovalent cations, X537A and monensin, occurred concomitantly with profound alterations of secretory granule structure (swelling and dissolution of the dense core). These results suggest that the effect of these drugs is due primarily to leakage of dopamine from granules to the cytoplasm and extracellular space. In contrast, the changes induced by other stimulatory drugs used concerned not the structure but the number of secretory granules, indicating that with these drugs stimulation of exocytosis is the phenomenon underlying the increased transmitter release. The release response induced by the Ca2+-ionophore ionomycin was dependent on [Ca2+]o, occurred rapidly, was concomitant with a marked rise of [Ca2+]i, and ceased after 1-2 min even though [Ca2+]i remained elevated for many minutes. 12-O-tetradecanoylphorbol, 13-acetate and diacylglycerol (both of which are known as activators of protein kinase C) induced slow responses almost completely independent of [Ca2+]o and not accompanied by changes of [Ca2+]i. Combination of an activator of protein kinase C with a low concentration of ionomycin failed to modify the [Ca2+]i rise induced by the ionophore, but elicited a marked potentiation of the release response, which was two- to fourfold larger than the sum of the responses elicited separately by either drugs. Thus, activation of protein kinase C seems to play an important role in the regulation of exocytosis in neurosecretory cells, possibly by increasing and maintaining the sensitivity to Ca2+ of the intracellular apparatus regulating granule discharge by exocytosis.

Adrenal Gland Neoplasms↗
PubMed1984

Supramaximal caerulein stimulation and ultrastructure of rat pancreatic acinar cell: early morphological changes during development of experimental pancreatitis.

Rats infused with a supramaximally stimulating dose of the cholecystokinin-pancreozymin analogue caerulein develop acute interstitial pancreatitis (M. Lampel and H.F. Kern. Virchows Arch. A 373: 97-117, 1977). We have studied the early (30-180 min) morphological changes in pancreatic acinar cells induced by infusing caerulein (2.5 micrograms X kg-1 X h-1). The techniques of thin-section electron microscopy, freeze fracture, and enzyme and immunocytochemistry were employed. Shortly (30 min) after the onset of caerulein infusion, large vacuoles appeared in the Golgi area. After longer periods of infusion, these vacuoles further enlarged (probably by fusion with other such vacuoles as well as autophagic vacuoles) and became more widely distributed in the cytoplasm. These large vacuoles were found to be acid phosphatase positive and to be labeled by antibodies directed against digestive zymogens as well as the lysosomal enzyme cathepsin D. These observations indicate that the large vacuoles contain both digestive zymogens and lysosomal hydrolases. During caerulein infusion, morphological evidence of exocytosis at the luminal plasmalemma was reduced or absent, and evidence of basolateral exocytosis was not noted. These studies suggest that secretagogue hyperstimulation with caerulein interferes with the processes involved in condensing vacuole maturation, which normally lead to the separation of digestive zymogens and lysosomal hydrolases. As a result, both types of enzymes remain within the same compartment. This may lead to the intracellular activation of digestive enzymes by lysosomal hydrolases and be an important step in the development of acute pancreatitis.

Acute Disease↗
PubMed1984

Alpha latrotoxin of black widow spider venom: an interesting neurotoxin and a tool for investigating the process of neurotransmitter release.

Alpha latrotoxin, purified from the venom of the black widow spider, is a high Mr (130000) protein devoid of detectable enzymatic activity. When applied to vertebrate nerve terminals (of the central as well as peripheral nervous systems) the toxin elicits massive release of neurotransmitters by stimulating the fusion of synaptic vesicles with the presynaptic membrane (exocytosis). Among non-neuronal systems, only the neurosecretory cell line PC12 is sensitive to alpha latrotoxin; all others investigated so far are insensitive. In order to act, alpha latrotoxin requires the presence of divalent cations in the medium. Ca2+ can be substituted by other divalent cations as Sr2+, Ba2+, Mn2+, Mg2+. However, with the last two the catecholamine release response is reduced in PC12 cells and synaptosomes. A specific, high affinity receptor of alpha latrotoxin exists in preparation sensitive to the toxin. This receptor has been purified and found to be a high Mr, integral membrane protein. In the frog neuromuscular junction the receptor is localized exclusively in the presynaptic membrane. Binding of alpha latrotoxin to the receptor in a Ca2+-containing incubation medium induces membrane depolarization (insensitive to tetrodotoxin), stimulation of Ca2+ influx (insensitive to verapamil) with consequent increase in the cytoplasmic free Ca2+ concentration and stimulation of phosphoinositide breakdown. In Ca2+ free medium depolarization is maintained, but free Ca2+ concentration does not rise after toxin application. In conclusion, alpha latrotoxin seems to act through a dual mechanism. The Ca2+-independent part of this mechanism may be mediated by the activation of protein kinase C, triggered by phosphoinositide metabolism. The relevance of these findings for presynaptic physiology is discussed.

Animals↗
PubMed1983

The effects of alpha-latrotoxin of black widow spider venom on synaptosome ultrastructure. A morphometric analysis correlating its effects on transmitter release.

The morphological effects of alpha-latrotoxin, the major component of black widow spider venom, were studied quantitatively in a crude synaptosome fraction (prepared from rat brain cortices) which was incubated at 37 degrees C for 10 min in Ringer solutions. Two toxin concentrations were employed, one causing a very large stimulation of transmitter release (approximately 65% and approximately 43% release of [3H]noradrenaline from preloaded synaptosomes, with and without Ca2+ in the incubation buffer), the other 50-60% as active. Incubated synaptosomes, fixed in suspension with aldehydes, were evenly dispersed in agarose before embedding, to assure randomized sampling in the subsequent morphometric analysis. In all the experimental conditions investigated, alpha-latrotoxin treatment caused a significant decrease in the density (number/unit area) of synaptic vesicles in synaptosome profiles. Such an effect was dose-dependent and partially Ca2+-dependent, in good agreement with the data on transmitter release. At high toxin concentration a moderate increase of synaptosome volume and surface area was observed, both with and without Ca2+. Mitochondrial swelling appeared only in synaptosomes treated in Ca2+ containing medium. These effects of alpha-latrotoxin are similar to those described previously at the neuromuscular junction. Thus, the toxin might be a tool of general use for studying vertebrate synapses.

Animals↗
PubMed1983

The effect of alpha-latrotoxin on the neurosecretory PC12 cell line: studies on toxin binding and stimulation of transmitter release.

alpha-Latrotoxin of black widow spider venom was found to bind with high affinity (KA = 1.8 X 10(9)M-1) to specific sites present in discrete number (approximately 6300/cell, approximately 12/micron2) at the surface membrane of PC12 cells. This binding correlated with (and therefore, probably caused) the secretory response produced by the toxin. Binding was enhanced (approximately 2-fold) in the presence of mM concentrations of various divalent cations (Ca2+, Mn2+ and Co2+) while Ba2+ and Sr2+ had a smaller effect and Mg2+ was inactive. Hypertonicity, concanavalin A and trypsin pretreatment of the cells blocked the binding interaction. The alpha-latrotoxin-induced stimulation of 3H-dopamine release was massive and occurred very rapidly when cells were exposed to the toxin in a Ca2+-containing Krebs-Ringer medium, whereas it occurred at a much slower rate in a Ca2+-free, Mg2+-containing Ringer. Introduction of Ca2+ into the latter medium resulted in a shift of the release rate from slow to fast. In contrast, in divalent cation-free medium the response was abolished. The toxin-induced secretory response was unaffected by Na+ and Ca2+ channel blockers (tetrodotoxin and D600) as well as by calmodulin inhibitors (calmidazolium and trifluoperazine). The effects of Ca2+ and Mg2+ were found to be concentration-dependent, with half maximal responses occurring at approximately 0.3 and 1.5 mM for the two divalent cations, respectively. Other divalent cations could substitute for Ca2+ and Mg2+, the relative efficacy being Sr2+ greater than Ca2+ greater than Ba2+ much greater than Mn2+ greater than Mg2+ greater than Co2+. Moreover, the response occurring at suboptimal concentration of Ca2+ (0.4 mM) was potentiated by the concomitant addition of either Mg2+, Mn2+ or Co2+. The effect(s) of divalent cations in supporting the alpha-latrotoxin-induced release response seem(s) to occur primarily at step(s) beyond toxin binding because (a) the stimulatory effects of the various cations on release were not matched by parallel effects on binding, and (b) Ca2+ maintained its ability to stimulate fast release even when toxin binding had occurred in a Ca2+-free medium. Delays in the release responses were observed when cells were exposed to alpha LTx in Na+-free, glucosamine or methylamine-based media, or depolarized with high K+ (in the presence of D600) before toxin treatment. Moreover, in these two conditions the ability of Mg2+ to support the alpha LTx response was considerably decreased.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

The effect of alpha-latrotoxin on the neurosecretory PC12 cell line: electron microscopy and cytotoxicity studies.

Neurosecretory PC12 cells were exposed in a variety of experimental conditions to nanomolar concentrations of alpha-latrotoxin purified from the venom of the black widow spider. When applied in a modified Ringer medium containing millimolar Ca2+ the toxin rapidly elicited a marked stimulation of exocytosis, as indicated by the appearance of typical images of granule-plasmalemma interaction and by the decreased density (number/unit area) of secretion granules in the cytoplasm. Without Ca2+ in the medium this early toxin effect was delayed and evolved less rapidly, but was still clearly appreciable. These morphological results appear in good quantitative agreement with the biochemical data on dopamine release reported in the preceding article. The stimulation of exocytosis was followed after a short delay by a stimulation of endocytosis, as revealed by an increased accumulation of the extracellular tracer, [14C]sucrose, within the toxin-treated cells. At later times after the application of alpha-latrotoxin other effects appeared, but only in the presence of Ca2+: these included changes in cell shape; focal alterations of the mitochondrial matrix (clear discrete areas and dense precipitates) and frank signs of cytotoxicity (rupture of the plasmalemma, clearing of the cytoplasmatic matrix). The toxin-induced cell death was studied quantitatively by using trypan blue exclusion as well as the 51Cr test, and was found to be dependent on alpha-latrotoxin concentration, temperature of incubation and Ca2+ concentration in the medium. Ionic substitutions concerning anions as well as cations other than Ca2+ had minor or no consequences. Thus, the early effect of alpha-latrotoxin in PC12 cells (stimulation of exocytosis, at least partially Ca2+-independent) can be dissociated from the late 'toxic' effect (strictly Ca2+-dependent).

Animals↗
PubMed1983

Experimental studies on the hypolipidemic activity of chloridarol.

The efficacy of chloridarol (2-benzofuryl-p-chlorophenyl carbinol) as hypolipidemic agent was evaluated in rats and rabbits. In normolipidemic rats chloridarol, at doses ranging from 50 to 200 mg/kg/day, decreased plasma triglycerides without affecting cholesterolemia and fast- or norepinephrine-induced lipolysis. The drug proved effective in reducing fructose-induced hypertriglyceridemia and dietary hypercholesterolemia in rats; in the latter model chloridarol significantly raised both the HDL cholesterol and the HDL/VLDL + LDL cholesterol ratio. In hyperlipidemic rabbits the drug had no effect on plasma cholesterol, but it lowered triglyceridemia. The action of chloridarol on rat liver ultrastructure was also investigated. Treatment for one month induced peroxisome proliferation, less marked, however, than that elicited by clofibrate; after a prolonged chloridarol treatment (9 months), this effect had almost completely disappeared and the ultrastructure of the hepatocytes was close to that of controls.

Animals↗
PubMed1982

Peripheral catecholamine release by alpha-latrotoxin in the rat.

Intraarterial injection of alpha-latrotoxin (alpha LTx), the major toxin of the black widow spider (Latrodectus mactans tredecimguttatus) venom, into carotid catheterized rats, induced prompt and marked rises in plasma adrenaline and noradrenaline concentrations, indicating that the toxin stimulates catecholamine release from both the adrenal medulla and sympathetic nerve terminals. Pretreatment with the ganglionic blocker chlorisondamine greatly reduced the plasma adrenaline response to alpha LTx but had almost no effect on the noradrenaline response, indicating that alpha LTx-stimulation of sympathetic nerve terminals is direct, whereas catecholamine release from the adrenal medulla is probably mediated by preganglionic release of acetylcholine. In vitro, alpha LTx induced a dose-dependent release of 3H-noradrenaline from rat irides preincubated with this radioactive amine and this effect was not changed by chlorisondamine plus atropine. By contrast, the toxin had no effect on 3H-noradrenaline release from suspensions of cultured rat chromaffin cells. Specific, high affinity binding of 125I-alpha LTx in iris and adrenal medulla homogenates was found to be exceedingly low, suggesting that it might be restricted to nerve terminals. No 125I-alpha LTx binding was seen nor could any effect of the toxin on 14C-5-hydroxytryptamine release be found in rat blood platelet preparations. alpha LTx binding and its amine releasing effect seem, therefore, to be specific for neurons and absent from other cells, even those, like adrenomedullary cells and blood platelets, which share with neurons their origin and/or other important characteristics.

Adrenal Medulla↗
PubMed1982

alpha-latrotoxin of black widow spider venom depolarizes the plasma membrane, induces massive calcium influx, and stimulates transmitter release in guinea pig brain synaptosomes.

The effect of alpha-latrotoxin from black widow spider venom upon guinea pig cerebral cortical synaptosomes is described. Plasma membrane potential (delta psi p), in situ mitochondrial membrane potential (delta psi m), Ca2+ transport, gamma-amino[3H]butyrate release, [3H]noradrenaline release, and synaptosomal ATP were monitored under parallel conditions. Potentials were determined both isotopically and with a tetraphenylphosphonium-selective electrode. alpha-Latrotoxin depolarizes delta psi p selectively, both in the presence and absence of Ca2+. A slight toxin-induced depolarization of delta psi m is a consequence of a massive Ca2+ uptake across the plasma membrane. Depolarization of delta psi p is insensitive to tetrodotoxin, and Ca2+ entry is only partially inhibited by verapamil. Release of [3H]noradrenaline and gamma-amino[3H]butyrate is markedly stimulated by the toxin in the presence of Ca2+, and this effect is only slightly reduced in Ca2+-free conditions.

Animals↗
PubMed1982

Studies on alpha-latrotoxin receptors in rat brain synaptosomes: correlation between toxin binding and stimulation of transmitter release.

alpha-Latrotoxin (alpha-LT), the major component of black widow spider venom, is a high-molecular-weight protein that acts presynaptically by stimulating the release of stored neurotransmitters. The purified toxin was iodinated to high specific radioactivity by the Bolton-Hunter procedure, without appreciable loss of biological activity. By the use of the 125I-toxin, specific receptors were revealed in synaptosome fractions isolated from various regions of the rat brain, but not in nonneural tissues. The density of alpha-LT receptors [which are probably composed of, or include, membrane protein(s)] varies between 0.6 and 0.88 pmol/mg of synaptosome protein, their affinity is very high (KA of the order of 10(10) M-1), their association rate is fast, and their dissociation rate slow. They might belong to a single, homogeneous class. This last conclusion, however, is still uncertain, because results suggesting a possible heterogeneity were obtained by studying the dissociation of the toxin from synaptosomes incubated in high-salt buffer. Experiments in which the binding of alpha-LT and its dopamine release activity in striatal synaptosomes were investigated in parallel in a variety of experimental conditions support the hypothesis that occupation of the high-affinity receptors is the initial step in the alpha-LT activation of the presynaptic response.

Animals↗
PubMed1982

Pancreatic effects of ethionine: blockade of exocytosis and appearance of crinophagy and autophagy precede cellular necrosis.

Young female mice fed a choline-deficient, ethionine-supplemented (CDE) diet for 24 h develop hemorrhagic pancreatic necrosis with a 5-day mortality rate of approximately 50%. At the end of the diet administration, the in vivo discharge of digestive enzymes is blocked, images of exocytosis and luminal membrane recycling disappear, and zymogen granules accumulate within acinar cells. The general ultrastructure, however, remains well preserved, protein synthesis is normal, and intracellular transport of secretory proteins is only slightly retarded. Thus, the CDE diet does not affect the general phenomenon of membrane fusion-fission but specifically inhibits that associated with exocytosis. Twenty-four hours after withdrawal of the CDE diet, discharge of zymogen granules into lysosomes (crinophagy) can be observed, and, 24 h latr, autophagocytosis is noted. Finally, shortly before the onset of pancreatic necrosis, cells of nearly normal appearance are noted to be scattered among cells showing varying degrees of lesion up to complete disruption. Thus, the CDE-induced pancreatic necrosis results from a sequence of events: blockade of exocytosis evolves to crinophagy and autophagy, which might lead to lysosomal activation of zymogens.

Animals↗
PubMed1981

Exocytosis and membrane recycling.

Exocytosis implies the fusion of the membrane of secretion granules with, and the insertion into, the plasmalemma. In non-growing systems such an insertion is temporary in that the inserted membrane is eventually removed. Turnover results indicate that the removed membrane is not destroyed but recycled within the cell and reused. In some systems exocytosis occurs over the entire plasmalemma, while in others it is restricted to discrete regions, characterized by peculiar morphology and composition. Thus the fusion of the two membranes is probably preceded by a recognition step. Structural specializations were detected in interacting granule and plasma membranes by freeze-fracture and surface labelling techniques: arrays of intramembrane particles in protozoans and nerve terminals; clearing of particles and surface antigens in other systems. Direct evidence, obtained in some secretory systems, indicates that after exocytosis the granules and plasma membranes do not intermix, but remain segregated. The subsequent recapture of membrane patches of the granule type (in many systems by means of coated pits and vesicles) could then account for the striking specificity of the recycling process, documented by both composition and structural studies. In different systems the recycling of granule membranes is carried out at greatly different rates. Recent results in the parotid gland and neuromuscular junction indicate that this process is Ca2+-dependent.

Animals↗