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C Vozzi

Publications and source records attributed to C Vozzi.

21 records · Page 2Linked to original sources

Adequate connexin-mediated coupling is required for proper insulin production.

To assess whether connexin (Cx) expression contributes to insulin secretion, we have investigated normal and tumoral insulin-producing cells for connexins, gap junctions, and coupling. We have found that the glucose-sensitive cells of pancreatic islets and of a rat insulinoma are functionally coupled by gap junctions made of Cx43. In contrast, cells of several lines secreting insulin abnormally do not express Cx43, gap junctions, and coupling. After correction of these defects by stable transfection of Cx43 cDNA, cells expressing modest levels of Cx43 and coupling, as observed in native beta-cells, showed an expression of the insulin gene and an insulin content that were markedly elevated, compared with those observed in both wild-type (uncoupled) cells and in transfected cells overexpressing Cx43. These findings indicate that adequate levels of Cx-mediated coupling are required for proper insulin production and storage.

Animals↗

Gap junctional communication of primary human keratinocytes: characterization by dual voltage clamp and dye transfer.

We have compared dye coupling in pairs of small (less than 10 microns in diameter) and large (greater than 20 microns in diameter) keratinocytes isolated from normal human epidermis, using Lucifer yellow microinjection. Under control conditions, dye coupling was found in only 1 out of the 25 small pairs tested, whereas it was evident in 75% of the large pairs (n = 52). After a 30-min incubation of the latter pairs in the presence of 10(-6) and 10(-4) M all-transretinoic acid (RA), the percentage of coupling was 53% (n = 15; NS) and 7% (n = 14; P less than 0.001), respectively. The almost complete uncoupling observed after 10(-4) M RA was not reversible even 30 min after return to control medium (n = 8). Dual whole-cell patch-clamp recordings from large keratinocyte pairs showed a macroscopic junctional conductance (gj) of 9 +/- 2 nS (n = 43), which was abolished by heptanol (3.5 mM) in a fully reversible way. Compared to heptanol, 10(-4) M RA abolished keratinocyte gj more slowly and irreversibly (n = 10). By contrast, 10(-6) M RA had no significant effect on gj (n = 8). Single-gap junctional channels were also identified between large keratinocytes. Events histograms of 152 transitions from three experiments revealed three main unitary conductances (gamma j) of 45 +/- 4, 78 +/- 4, and 106 +/- 7 pS. The dye coupling results indicate that junctional communication is markedly different in pairs of small and large cells, which showed the phenotype and keratin markers of basal and suprabasal keratinocytes, respectively. In the latter cell type, coupling is ensured by channels of three sizes and is blocked irreversibly by pharmacologic concentrations of RA.

Alcohols↗

Thyrotropin-releasing hormone causes direct excitation of dorsal vagal and solitary tract neurones in rat brainstem slices.

The effect of thyrotropin-releasing hormone (TRH) on neurones in the dorsal motor nucleus of the vagus and the nucleus of the solitary tract was studied using extracellular single-unit recordings from brainstem slices of the rat. About one third of vagal neurones were excited by TRH. The remaining neurones were unaffected. The lowest effective peptide concentration was around 10 nM and a half maximal effect was achieved at about 100 nM. The action of TRH persisted in a low-calcium, high-magnesium solution which blocks synaptic transmission. The biologically inactive compound, TRH-free acid, was without effect. In the nucleus of the solitary tract, one fourth of the neurones were excited by TRH; none were inhibited by this peptide. Part of the vagal TRH-responsive neurones were also excited by oxytocin and some of the solitary tract neurones sensitive to TRH also responded to vasopressin. We conclude that a fraction of neurones located in the dorsal motor nucleus of the vagus and the nucleus of the solitary tract possess functional TRH receptors. TRH may thus act as a neurotransmitter or neuromodulator in the dorsal brainstem and may participate in the regulation of autonomic functions.

Animals↗