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Biomedical subjects

L Zilletti

Publications and source records attributed to L Zilletti.

At least 55 records · Page 3Linked to original sources
PubMed1985

Modulatory activity of GABAB receptors on cholinergic tone in guinea-pig distal colon.

The effect of gamma-aminobutyric acid (GABA) administration was studied in both in vitro and in vivo preparations of the guinea-pig distal colon. In in vitro preparations GABA (10(-7) - 10(-3) M) elicited a dose-dependent relaxation; a decrease in the spontaneous contractions was sometimes observed. The effect of GABA was mimicked by (-)-baclofen, which gave a dose-response curve overlapping that of GABA, while (+)-baclofen was about one hundred times less potent. The relaxation responses induced by the above drugs were antagonized by 5-aminovaleric acid (5 X 10(-4) M), which did not affect adenosine-induced relaxation, but they were insensitive to bicuculline (10(-5) M) and picrotoxin (10(-5) M). Moreover, they were prevented by tetrodotoxin (6 X 10(-7) M). In hyoscine (10(-7) M)-pretreated preparations, GABA still evoked a small relaxation response (approx. 10% of the maximum) that was bicuculline-sensitive. Desensitization to GABA (10(-5) M) was observed. A specific cross-desensitization occurred between GABA (10(-5) M) and (-)-baclofen (10(-5) M). In in vivo preparations, GABA (10 mumol kg-1) and (-)-baclofen (5 mumol kg-1) produced a dose-related inhibition of basal tone, while (+)-baclofen (5 mumol kg-1) had much less effect (about 25%). A decrease in the spontaneous contractions was sometimes observed. The relaxant effect of GABA and (-)-baclofen persisted in guinea-pigs pretreated (1-2 min) with picrotoxin (1.6 mumol kg-1), whereas it was significantly reduced in animals injected 1 min beforehand with 5-aminovaleric acid (0.2 mmol). The maximal relaxant effect induced by GABA and (-)-baclofen did not differ from that of atropine (0.9 mumol kg-1) and after atropine administration GABA had no further inhibitory effect. Relaxation responses induced by GABA and (-)-baclofen still occurred after blockade of nicotinic receptors by hexamethonium (0.17 mmol kg-1), which itself caused an increase in the basal tone. When the tone was increased by topical application of physostigmine (40 micrograms), GABA and (-)-baclofen induced a greater relaxation than that obtained in basal conditions. It is concluded that GABA, both in vitro and in vivo administration, inhibits cholinergic tone in guinea-pig distal colon and that this effect is mediated mainly by activation of GABAB receptors. Further experiments are required to ascertain the possible physiological role of a GABA-releasing neuronal system in the colon in vivo.

Amino Acids↗
PubMed1984

Influence of GABA on anaphylactic histamine release in vitro.

In this preliminary report an unreported inhibitory action of GABA on anaphylactic reaction has been described. In a functional model (Schultz-Dale reaction) GABA has been demonstrated to inhibit the antigen-evoked contraction. This effect depends on a modulation of anaphylactic histamine release. The phenomenon is dose-dependent and requires a period of time to develop. Since GABAergic neurons are present in the preparation, it is possible to speculate that GABA receptors are involved in this inhibitory action. However, pharmacological analysis of the phenomenon has to be carried out, especially in view of the latency of GABA to develop its effect.

Anaphylaxis↗
PubMed1983

GABAA and GABAB receptor-mediated effects in guinea-pig ileum.

1 The effects of gamma-aminobutyric acid (GABA) and related substances were examined in guinea-pig ileum longitudinal muscle.2 GABA at doses ranging from 10(-7) M to 3 x 10(-6) M elicited a relaxation while at higher doses (3 x 10(-6) M - 10(-4) M), as previously described, it caused a contraction followed by relaxation.3 GABA-induced relaxation was bicuculline-insensitive, was mimicked by (-)-baclofen but not by homotaurine and muscimol. The effect of baclofen was stereospecific. GABA- and (-)-baclofen-induced relaxations were dose-dependent and their ED(50) values were similar. A specific cross-desensitization occurred between GABA and (-)-baclofen.4 The bicuculline-insensitive relaxation induced by GABA and (-)-baclofen was prevented by tetrodotoxin and hyoscine but not by phentolamine plus propranolol, naloxone or theophylline.5 In preparations in which the muscle tone was raised by histamine or prostaglandin F(2alpha), GABA and (-)-baclofen induced relaxation to the same extent as before increasing the tone. If the tone was raised by DMPP, a greater bicuculline-insensitive relaxation occurred.6 Contraction caused by GABA was bicuculline-sensitive and was mimicked by homotaurine and muscimol. Contraction was dose-dependent and muscimol was about three times more potent than GABA or homotaurine. A specific cross-desensitization occurred between the contractile effects of GABA and those of homotaurine or muscimol.7 Bicuculline competitively antagonized the contractile effects of GABA, homotaurine and muscimol and gave closely similar pA(2) values. The slope of the Schild plot for the above drugs was near 1, confirming the competitive nature of the antagonism.8 The bicuculline-sensitive contraction induced by GABA, homotaurine and muscimol was abolished by tetrodotoxin and was non-competitively antagonized by hyoscine, while it was unaffected by hexamethonium, mepyramine and methysergide.9 It is concluded that two receptors mediate the GABA effects in guinea-pig ileum: a bicuculline-sensitive GABA(A) receptor, which elicits contraction through an excitatory action on cholinergic post-ganglionic neurones; and a bicuculline-insensitive GABA(B) receptor which causes relaxation through an inhibitory presynaptic action on cholinergic post-ganglionic neurones. We confirm that GABA, homotaurine and muscimol are GABA(A) agonists, while GABA and (-)-baclofen are GABA(B) agonists.

Animals↗
PubMed1983

Homotaurine: a GABAB antagonist in guinea-pig ileum.

Homotaurine (3-aminopropane sulphonic acid) did not inhibit the twitch response in guinea-pig ileum longitudinal muscle whilst gamma-aminobutyric acid (GABA) and (-)-baclofen evoked dose-dependent inhibitions. The inhibitory effects of GABA and (-)-baclofen were prevented in the presence of homotaurine 2 X 10(-4) and 10(-3) M. The log dose-effect curves of GABA and (-)-baclofen were shifted in a parallel manner compatible with competitive antagonism. The pA2 of homotaurine with GABA (4.22 +/- 0.05) and (-)-baclofen (4.26 +/- 0.1) were the same. Homotaurine did not antagonize the inhibitory effects of morphine (ED50 4 X 10(-7) M), noradrenaline (ED50 10(-6) M) or ATP (ED50 1.5 X 10(-5) M). The inferior homologue of homotaurine, taurine 10(-3) M, did not modify the inhibitory effects of GABA and (-)-baclofen. Picrotoxin 5 X 10(-5) M antagonized GABAA receptor-mediated contraction but did not affect GABAB receptor-mediated inhibition. At the same concentration the drug did not influence the antagonistic action of homotaurine, thus showing no GABAA receptor-mediated interference. It may be concluded that homotaurine is a competitive antagonist of GABAB mediated effects in the guinea-pig ileum.

Animals↗
PubMed1982

Effect of taurine on calcium levels and contractility in guinea-pig ventricular strips.

Taurine increases the calcium levels in guinea-pig ventricular strips at external calcium concentrations of 0.45, 0.9 and 1.8 mM. At 2.7 mM calcium, however, a decrease is observed. Analogous changes occur in contractile force. It is also seen that the superfusion of ventricular strips with taurine-free medium produces a decrease in taurine content at the end of 120 min superfusion. Taurine levels can be restored by superfusion with 10 mM taurine; a linear relationship exists between external taurine and internal taurine levels.

Animals↗
PubMed1982

Presence of functionally active beta-adrenoceptors in rat mast cells. Correlation between (--)[3H]-dihydroalprenolol binding and inhibition of histamine release.

The correlation between the binding of a beta-adrenoceptor antagonist, (--)[3H]-dihydroalprenolol (DHAP), and the adrenergic inhibition of histamine release by acetylcholine and by compound 48/80 was studied with isolated purified rat mast cells and in rat mast cell crude membrane fractions. Acetylcholine-evoked histamine release was inhibited by catecholamines, in the order isoprenaline greater than adrenaline greater than noradrenaline. Pretreatment of cells with (--)alprenolol antagonized the inhibitory effect of isoprenaline on acetylcholine-induced histamine release. 40/80-evoked histamine release was blocked by isoprenaline at significantly higher concentrations than those required to inhibit cholinergic histamine release. The inhibitory effect of isoprenaline was equally antagonized by preincubating mast cells with (--)alprenolol. Specific binding sites for DHAP have been demonstrated in rat mast cell membranes. The specific binding of DHAP was inhibited by adrenoceptor agonists and antagonists according to the stereospecificity of these compounds. A close correlation between the binding-inhibitory potency of various adrenergic compounds and the data obtained in the pharmacological experiments was found, thus indicating the presence of beta-adrenoceptors in rat mast cells.

Acetylcholine↗
PubMed1982

The effect of taurine on high potassium-and noradrenaline-induced contraction in rabbit ear artery.

1 Intraluminal administration of taurine (40 mM) did not affect the contractile tone of rabbit isolated ear artery 2 Taurine (10-80 mM) exerted a powerful concentration-dependent, vasodilator action in arteries contracted with high potassium medium. 3 In the same experimental conditions, the taurine analogues beta-alanine and homotaurine, had no effect. 4 Taurine (40-80 mM) did not affect in a significant manner the tonic component of the noradrenaline (5x10(-6 M)-induced contraction. 5 When noradrenaline (5x10(-6M) was followed by the administration of high potassium medium a further increase in intraluminal pressure was observed. Under these conditions taurine (40 mM) reversed specifically the component due to the high potassium medium.

Alanine↗
PubMed1980

[Mechanism of action of butylhydroxyanisole (BHA) toxicity: in vivo and in vitro effects on mammalian smooth muscle].

The toxicity of butylated hydroxyanisole (BHA) was greatly enhanced in the rat after i.p. administration, the LD50 being two orders of magnitude higher than the oral administered dose. The compound was shown either "in vitro" or "in vivo" to impair the smooth muscle contractility. Study on the mechanism of toxic action of Butylated hydroxyanisole (BHA): "in vivo" and "in vitro" effects on mammalian smooth muscle.

Animals↗
PubMed1980

Inhibition of cholinergic histamine release in rat mast cells.

Adrenaline inhibits the acetylcholine-evoked histamine release from isolated purified rat mast cells, in a dose-dependent fashion. The inhibitory effect of adrenaline is reversed by preincubating the cells with a beta-blocker, aprenolol, but not by preincubating them with an alpha-blocker, phentolamine. These results were confirmed by observations using an electron microscope and they suggest that adrenaline inhibits the cholinergic histamine release from rat mast cells acting upoon beta-receptors.

Acetylcholine↗