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G Fontana

Publications and source records attributed to G Fontana.

At least 73 records · Page 4Linked to original sources
PubMed1991

gamma-Aminobutyric acid (GABA) stimulates somatostatin release following activation of a GABA uptake carrier located on somatostatin nerve endings of rat cerebral cortex.

The effect of gamma-aminobutyric acid (GABA) on the release of somatostatin-like immunoreactivity (SRIF-LI) was studied in synaptosomes prepared from rat cerebral cortex and exposed in superfusion to the amino acid. GABA (1-300 microM) increased the spontaneous outflow of SRIF-LI in a concentration-dependent manner. The effect of GABA was not prevented by the GABAA receptor antagonists bicuculline or picrotoxin. The GABAA receptor agonist muscimol (10-100 microM) did not affect SRIF-LI release. Similarly ineffective was the GABAB receptor agonist (-)-baclofen (100 microM). The GABA-induced SRIF-LI release was counteracted by the GABA uptake inhibitors N-(4,4-diphenyl-3-butenyl)-nipecotic acid (SK&F 89976A) and nipecotic acid. When used as a GABA carrier substrate, nipecotic acid mimicked GABA and increased SRIF-LI release; its effect was antagonized by SK&F 89976A. The mechanism involved appears to be selective for GABA inasmuch as neutral amino acids such as leucine, alpha-aminobutyric acid or valine, tested at 100 microM, had little or no effect on the release of SRIF-LI. Neither GABA (100 microM) nor nipecotic acid (300 microM) enhanced the release of cholecystokinin-like immunoreactivity. The GABA-evoked somatostatin release was calcium-dependent and tetrodotoxin-insensitive. It is concluded that a carrier for the uptake of GABA exists on somatostatin-releasing terminals of rat cerebral cortex and that GABA uptake may regulate somatostatin release. This conclusion would be compatible with the reported coexistence of GABA and somatostatin in cerebrocortical neurons.

Amino Acids↗
PubMed1991

gamma-Aminobutyric acidB receptors mediate inhibition of somatostatin release from cerebrocortex nerve terminals.

The effects of gamma-aminobutyric acid (GABA) and of various GABA receptor agonists and antagonists on the calcium-dependent depolarization-evoked release of somatostatin (SRIF) from rat cerebrocortex synaptosomes have been studied by a superfusion technique. GABA (0.3-30 microM) decreased the K+ (15 mM)-evoked overflow of SRIF-like immunoreactivity (SRIF-LI) in a concentration-dependent manner (EC50 = 1.3 microM; maximal inhibition, 45% reached at 10 microM GABA). The effect of the amino acid was insensitive to the GABAA receptor antagonist bicuculline. Accordingly, the K(+)-evoked SRIF-LI release was not affected by muscimol, a GABAA receptor agonist, up to 100 microM. The effect of GABA was mimicked by the GABAB receptor agonist (-)-baclofen (EC50 = 1.2 microM; maximal effect, about 45% reached at 10 microM). The effect of baclofen was stereoselective, the (+)-enantiomer being inactive up to 100 microM. The inhibition of SRIF-LI release brought about by GABA was sensitive to the GABAB receptor antagonists 2-hydroxy-saclofen and CGP 35348 [3-aminopropyl(diethoxymethyl)phosphinic acid]. Also, the effect of (-)-baclofen was antagonized by CGP 35348 (IC50 = 4.8 microM). It is concluded that GABA can inhibit the depolarization-evoked release of SRIF by activating receptors which are located on SRIF-releasing nerve terminals and belong to the GABAB type.

Animals↗
PubMed1991

Exocrine pancreatic involvement in Wegener's granulomatosis. A case report.

A rare case of exocrine pancreatic damage in a patient with Wegener's granulomatosis is reported. The pancreatic amino acid consumption test, a new tubeless technique, revealed exocrine pancreatic insufficiency before and after immunosuppressive therapy. The presence of exocrine pancreatic insufficiency in this patient raises the possibility of pancreatic involvement in Wegener's granulomatosis.

Aged↗
PubMed1991

[Myocardial involvement in rhabdomyolysis caused by acute heroin intoxication].

It is well known that heroin overdose may cause rhabdomyolysis. Sometimes a myocardial involvement complicates its course. We report a case of heroin intoxication followed by rhabdomyolysis associated with myocardial injury, with symptoms, laboratory findings, ECG and echocardiography features of non-Q wave infarction. However, a 201 Tl myocardial scintigraphy, performed after patient discharging, did not show any abnormality. We think that heroin has a direct myotoxic effect on both myocardium and skeletal muscle. Yet we cannot exclude that hypoxia, acidosis, vasoconstrictive substances released by muscle necrosis, or hypersensitivity reactions associated with heroin or some of its adulterants are involved in myocardial injury.

Acute Disease↗
PubMed1990

Expiration-related neurons in the caudal ventral respiratory group of the cat: influences of the activation of Bötzinger complex neurons.

The functional role of Bötzinger complex (Böt. c.) projections to the expiration-related (ER) area of the caudal ventral respiratory group (cVRG) was investigated in anesthetized, vagotomized, paralyzed and artificially ventilated cats. ER neurons in both the ipsi- and the contralateral cVRG displayed excitatory responses to Böt. c. electrical microstimulation. They were also activated by microinjections of D,L-homocysteic acid into the Böt. c. region. We propose that at least part of the Böt. c. projections to the cVRG have an excitatory function.

Animals↗
PubMed1990

Glycine enhances [3H]noradrenaline release from slices of rat hippocampus.

The effects of glycine on the release of [3H]noradrenaline ([3H]NA) have been investigated using rat hippocampus slices previously labeled with the radioactive catecholamine. Glycine (30-1000 microM) produced a potent and concentration-dependent increase of the release of [3H]NA evoked by 12 mM KCl. The effect of 1000 microM glycine was totally antagonized by 3 microM strychnine suggesting that, in rat hippocampus, glycine may regulate the release of NA by activating a receptor of the strychnine-sensitive subtype.

Animals↗
PubMed1990

Glycine stimulates [3H]noradrenaline release by activating a strychnine-sensitive receptor present in rat hippocampus.

Rat hippocampus slices were prelabeled with [3H]noradrenaline ([3H]NA) and depolarized by superfusion with KCl. The release evoked by 12 mM K+ was totally calcium-dependent and more than 90% tetrodotoxin (TTX)-sensitive. Glycine (0.1-1 mM) increased the K(+)-evoked [3H]NA overflow in a concentration-dependent manner. The effect of 1 mM glycine reached 300%. Strychnine (0.3 microM) shifted to the right the concentration-response curve for glycine. The effect of glycine (0.1 or 1 mM) was totally abolished by 3 microM strychnine but was unaffected by the GABAA receptor antagonist, bicuculline (10 microM), or by 100 microM of 1-hydroxy-3-aminopyrrolidone-2 (HA-966), a proposed antagonist of glycine at the strychnine-insensitive site located on the N-methyl-D-aspartate (NMDA) receptor. The effect of glycine was mimicked by L-serine, although less potently; the release of [3H]NA was enhanced by 200% in presence of 3 mM L-serine. At this concentration D-serine was ineffective. Strychnine shifted to the right the concentration-response curve for L-serine. Glycine (1 mM) had only a minor effect (less than 20% potentiation) on the release of [3H]NA evoked by 12 mM KCl in hippocampal synaptosomes. While the effect of glycine in slices was increased by decreasing the depolarizing concentration of K+ (about 500% potentiation at 9 mM K+), the response of synaptosomes remained minimal, even in presence of 9 mM KCl. Hippocampal synaptosomes prelabeled with [3H]glycine released the radiolabeled amino acid when exposed to superfusion with 12 mM KCl. The release of [3H]glycine was more than 75% calcium-dependent. The results suggest that the release of NA in rat hippocampus may be enhanced by glycine through the activation of a strychnine-sensitive receptor. This receptor does not seem to be located on noradrenergic terminals.

Animals↗
PubMed1989

GABAB autoreceptors in rat cortex synaptosomes: response under different depolarizing and ionic conditions.

Rat cerebral cortex synaptosomes prelabeled with [3H]gamma-aminobutyric acid [( 3H]GABA) were exposed in superfusion to various concentrations of KCl (9-50 mM). The evoked release of [3H]GABA reached a plateau at about 35 mM KCl. The K+-induced release was Ca2+-dependent, particularly at the lowest K+ concentrations. The GABAB agonist (-)-baclofen concentration dependently inhibited the release of [3H]GABA evoked by K+; this effect decreased with increasing K+ concentration and disappeared at 35 mM KCl. The GABAA agonist muscimol (1-100 microM) was totally ineffective to inhibit the release of [3H]GABA. Veratrine (1-30 microM) induced the release of [3H]GABA and the effect was tetrodotoxin-sensitive. (-)-Baclofen, but not muscimol, decreased the veratrine-induced [3H]GABA release; the GABAB agonist was particularly effective in presence of low concentrations of veratrine (1-3 microM) but the effect disappeared when 30 microM of the alkaloid was used. The inhibitory effect of (-)-baclofen on the release of [3H]GABA evoked by 15 mM KCl was dependent on the concentration of Ca2+: the effect increased as the concentration of Ca2+ was raised, reaching a plateau at 0.6 mM Ca2+. Exogenous GABA, in presence of the GABA uptake blocker SK & F 89976A, inhibited the release of [3H]GABA evoked by K+; this effect was antagonized by phaclofen. The data support the idea that terminal GABA autoreceptors in the rat cerebral cortex are of the GABAB type.

Animals↗
PubMed1989

Presynaptic mechanisms underlying the gamma-aminobutyric acid-evoked receptor-independent release of [3H]norepinephrine in rat hippocampus.

The effects of gamma-aminobutyric acid (GABA) on the spontaneous efflux of [3H]norepinephrine ([3H]NE) were studied in synaptosomes prepared from rat hippocampus and prelabelled with [3H]NE. It had been observed previously that, when synaptosomes were exposed in superfusion to GABA, the basal release of the tritiated catecholamine was enhanced, apparently with no involvement of the known GABA receptors. The mechanisms underlying this effect have now been investigated. The potency of GABA as a releaser of [3H]NE was decreased by lowering the Na+ content of the superfusion medium, and its effect disappeared at 23 mM Na+. The GABA-induced [3H]NE release was counteracted by the GABA uptake inhibitor N-(4,4-diphenyl-3-butenyl)nipecotic acid (SKF 89976A), but it was unaffected by the NE uptake blockers desmethylimipramine and nisoxetine. The GABA-induced release of [3H]NE was Ca2+-dependent and tetrodotoxin-sensitive. The data support the hypothesis that GABA provoked [3H]NE release by a novel mechanism which involves penetration into the noradrenergic nerve terminals through a GABA carrier located on the NE terminals themselves. This uptake process might be electrogenic and provoke depolarization of the nerve terminals, causing an exocytotic release of [3H]NE.

Animals↗
PubMed1988

Effects of electrical and chemical stimulation of the Bötzinger complex on respiratory activity in the cat.

The effects of electrical and chemical stimulation of the expiratory neuronal population in the region of the retrofacial nucleus, the so called 'Bötzinger complex' (Böt. c.), on respiratory activity were investigated in vagotomized cats under pentobarbitone anaesthesia. Some of the experiments were performed on paralyzed or bilaterally thoracotomized, artificially ventilated animals. Sustained tetanic electrical stimulation (20 to 100-Hz, 0.5-ms current pulses at intensities of 5-60 microA) induced strong depressant effects on the inspiratory motor output which could lead to complete apnoea. The apnoeic response was accompanied by tonic activation of expiratory muscles; the appearance and the strength of tonic expiratory activity were dependent upon the frequency of stimulation. Brief tetani (40 to 100 ms trains of 0.5-ms rectangular pulses at 100-300 Hz) timed either during the inspiratory or the expiratory phase caused depression of inspiratory activity and prolongation of expiratory time, respectively. These effects increased gradually as the onset of stimulation was progressively delayed during each respiratory phase. The effects of sustained tetanic stimulation were mimicked by microinjections (25-100 nl) of 0.5 M L-glutamate or 0.16 M DL-homocysteic acid in the same region, thus indicating that they were the result of the stimulation of cell bodies and not of axons of passage. The present results support the hypothesis that Böt. c. neurons play an important role in the control of the breathing pattern by exerting inhibitory influences on inspiratory activity and, possibly, by contributing to the off-switch mechanisms. Furthermore, they suggest that these neurons are involved in the central control of expiratory activity.

Animals↗
PubMed1988

The activation of phosphatidylinositol turnover is not directly involved in the modulation of neurotransmitter release mediated by presynaptic muscarinic receptors.

In the rat cerebral cortex, the comparative effects of various muscarinic agonists on the release of [3H]dopamine ([3H]DA), [3H]acetylcholine ([3H]ACh), and [3H]5-hydroxytryptamine ([3H]5-HT) from superfused nerve endings and on phosphatidylinositol (PI) turnover were studied. Acetylcholine (ACh) was found to be the most potent among the agonists tested on all three release systems examined, and also on the activation of PI turnover. Oxotremorine and bethanechol were very weak agonists when tested as stimulators of PI turnover. However, oxotremorine was very effective as a release modulator, while bethanechol was completely ineffective. Our data suggest that the activation of PI turnover is not directly involved in the modulation of neurotransmitter release mediated by presynaptic muscarinic receptors.

Acetylcholine↗
PubMed1988

Influences of superior laryngeal afferent stimulation on expiratory activity in cats.

The effects of superior laryngeal nerve (SLN) stimulation on the activity of the expiratory muscles and medullary expiration-related (ER) neurons were investigated in 24 pentobarbital-anesthetized cats. In some experiments the animals were also paralyzed and artificially ventilated. Sustained tetanic stimulation of SLN consistently caused an apneic response associated with the appearance of tonic CO2-dependent activity in the expiratory muscles and in ER neurons located in the caudal ventral respiratory group (VRG) and the Bötzinger complex. Single shocks or brief tetani at the same stimulation intensities failed to evoke excitatory responses in the expiratory muscles and in the vast majority of ER neurons tested. At higher stimulation strengths, single shocks or short tetani elicited excitatory responses in the expiratory muscles (20- to 35-ms latency) and in the majority of ER neurons of the caudal VRG (7.5- to 15.5-ms latency). These responses were obtained only during the expiratory phase and proved to be CO2 independent. On the contrary, only inhibitory responses were evoked in the activity of Bötzinger complex neurons. The observed tonic expiratory activity most likely represents a disinhibition phenomenon due to the suppression of inspiratory activity; activation of expiratory muscles at higher stimulation intensities appears to be a polysynaptic reflex mediated by ER neurons of the caudal VRG but not by Bötzinger complex neurons.

Animals↗