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N Sopranzi

Publications and source records attributed to N Sopranzi.

30 records · Page 2Linked to original sources

Effects of bombesin on erythropoietin production in the anaesthetized dog.

Bombesin, a tetradecapeptide isolated from the skin of some European discoglossid frogs, has been reported previously to reduce renal blood flow and glomerular filtration rate and to increase plasma renin activity in anaesthetized dogs. In the present study bombesin was infused intravenously in anaesthetized dogs at dose levels of 3, 6 and 12 ng/kg/min for 6 h and renal blood flow, glomerular filtration rate, oxygen consumption, oxygen extraction by the kidney tissue, as well as plasma erythropoietin levels (ESF) and plasma renin activity were measured. Plasma levels of ESF increased during bombesin infusion only when renal blood flow was reduced to a level of 1 ml/g/min or less. In this situation glomerular filtration was blocked, renal oxygen consumption was decreased to 10% of normal and oxygen extraction by the kidney was increased by 2 times. No correlation was found between plasma renin activity and ESF concentrations during bombesin infusion. It is concluded that the stimulant action of bombesin on ESF production is a consequence of the renal hypoxia induced by the reduction in renal blood flow.

Animals↗

Parallel bioassay of bombesin and litorin, a bombesin-like peptide from the skin of Litoria aurea.

The spectrum of biological activity exhibited by litorin, a bombesin-like nonapeptide found in extracts of the skin of the Australian leptodactylid frog Litoria aurea was compared with that exhibited by the tetradecapeptide bombesin. 2 Litorin proved to be more potent than bombesin on isolated smooth muscle preparations and on the urinary bladder in situ. However, it was less potent on dog systemic blood pressure and kidney vasculature activation of the renen-angiotensin system being slight or lacking. 3 Gastrin release and acid secretion produced by litorin was more rapid in onset but less intense and less sustained than that elicited by bombesin. The same could be observed for pancreatic secretion. 4 Gall bladder contraction stimulated by litorin was probably caused by a double action of the peptide, directly on the bladder smooth muscle, and indirectly by cholecystokinin release. 5 In its effects on the myo-electric activity of the dog duodenum (inhibition of spikes and increase in frequency of pacesetter potentials leading to the appearance of a sequence of slow and small potentials) litorin possessed approximately 50 to 70% of the activity of bombesin.

Action Potentials↗

Gastrin release by bombesin in the dog.

1 The intravenous infusion of bombesin produced in intact dogs and, more strikingly in dogs provided with gastric fistulae a sharp increase in plasma levels of immunoreactive gastrin and at the same time a stimulation of gastric acid secretion. Gastrin response was correlated with the dose of bombesin from approximately 0.1 mug kg(-1) h(-1) (threshold) to 1 mug kg(-1) h(-1) (maximum gastrin release).2 Atropine and metiamide reduced or inhibited gastric acid secretion stimulated by bombesin, but did not affect the rise in gastrin levels.3 Acidification of the whole stomach or of a perfused antral pouch caused a reduced or delayed response to bombesin. However, the inhibitory effect of acidification could be surmounted by prolonging the duration of bombesin infusion.4 Antrectomy greatly reduced the rise in gastrin levels and the increase in acid gastric secretion produced by bombesin, but left unaffected the gastric secretagogue effect of pentagastrin.5 It is concluded that bombesin is a potent releaser of gastrin from the antral mucosa.6 The possible influence of the renal effects evoked by bombesin in the dog on the gastrin response to the polypeptide is discussed.

Animals↗

Evidence of cholecystokinin release by bombesin in the dog.

1 The intravenous infusion of bombesin elicited in the dog a contraction of the gall bladder with decreased opening pressure of the choledocho-duodenal junction and stimulation of pancreatic secretion.2 The pancreatic juice produced under the influence of bombesin was poor in bicarbonate and rich in protein. Threshold doses of the peptide were of the order of 0.25 mug kg(-1) h(-1) and maximum protein output was obtained with 1 mug kg(-1) h(-1). The pancreatic protein response to bombesin was very similar, in its onset and duration, to that elicited by intraduodenal infusion of L-tryptophan. Infusions of bombesin repeated at short intervals produced tachyphylaxis.3 Antrectomy did not affect the stimulant action of bombesin on the pancreas. Atropine however, reduced the pancreatic protein response to bombesin.4 It is suggested that bombesin acts on the gall bladder and the exocrine pancreas through release of cholecystokinin from the duodenal mucosa. No release of secretion could be demonstrated. It is likely that the releasing activity of bombesin is limited, in the field of gastrointestinal peptides, to those belonging to the gastrin-cholecystokinin family.

Animals↗

The action of bombesin on the kidney of the anaesthetized dog.

1. In the anaesthetized dog bombesin had a potent antidiuretic effect, and sometimes arrested urine flow completely. Threshold doses, by i.v. infusion, were of the order of 0.5-1 (ng/kg)/minute. Antidiuresis was the result of a reduction in glomerular filtration rate provoked by a fall in intraglomerular hydrostatic pressure. This, in its turn, was due to afferent vasoconstriction.2. The spasmogenic effect of bombesin on the smooth muscle of the afferent arterioles was directly demonstrated by the radioactive microspheres technique and indirectly by the (85)Kr washout method and by [(3)H]-p-aminohippurate clearance. The vascular compartment most sensitive to bombesin was that of the outer cortical zone, especially in its external half.3. Filtration fraction decreased under the influence of bombesin, indicating that the effect of the polypeptide on postglomerular arterioles was, if present, only of minor importance.4. At high infusion rates (above 6 (ng/kg)/min), bombesin produced a decrease in [(3)H]-p-aminohippurate extraction. The effect of the polypeptide on fractional distal delivery of sodium varied with the dose: at moderate infusion rates it decreased, at high infusion rates it increased. The total glucose appearing in urine following a glucose load was sharply reduced by bombesin. However, the glomerular filtration rate/maximum tubular glucose transport ratio did not show any appreciable change.5. Afferent vasoconstriction produced by bombesin was accompanied by an intense activation of the renin-angiotensin system, as shown by a conspicuous increase in renin secretion, followed by increases in renin activity and angiotensin II concentration in arterial blood. When bombesin was infused into one renal artery only the infused kidney showed afferent vasoconstriction and increased renin secretion. The time-course of renin secretion produced by bombesin depended upon the rate of infusion of the polypeptide. At low rates an increased renin secretion was observed throughout the infusion period, at high rates two peaks of renin secretion could be seen, one at the beginning of the infusion, the other soon after the infusion had finished.6. The mechanism of action of bombesin is discussed and the interest of the polypeptide as a possible hormonal regulator of the circulation and function of the kidney is pointed out.

Anesthesia, General↗

The action of bombesin on the systemic arterial blood pressure of some experimental animals.

1. The changes in blood pressure in response to parenteral administration of bombesin, the active tetradecapeptide of the skin of the European discoglossid frogs Bombina bombina and Bombina variegata variegata have been investigated in some experimental animals.2. In most species, the polypeptide elicited hypertension which was usually gradual in onset and slow to disappear. Blood pressure increases rarely exceeded 40-50 mmHg. At the beginning of an experiment some dose-response relationship could often be observed, but later tachyphylaxis developed. During an intravenous infusion of bombesin the rise in blood pressure could sometimes be maintained at a steady level as long as the infusion was continued, but at other times, the rise of pressure slowly subsided with continued administration of the polypeptide. In the rat and the chicken hypertension elicited by high doses of bombesin was often followed by secondary hypotension.3. Bombesin-induced hypertension was apparently not affected by pretreatment with either alpha- or beta-adrenergic blocking agents. Similarly secondary hypotension was not abolished by atropine. Thus, the effect of bombesin on vascular smooth muscle seems to be predominantly a direct one.4. Angiotensin was usually more potent than bombesin, and its effect on blood pressure was more rapid and of shorter duration. Tachyphylaxis to angiotensin was lacking or moderate.5. In sharp contrast to the other species, the monkey responded to bombesin with frank hypotension, which was usually proportional to the dose. In the monkey the hypotensive effect of bombesin was equal to, or greater than that of eledoisin or physalaemin and bombesin-induced hypotension was of longer duration than that of the other polypeptides. Tachyphylaxis was moderate for low and adequately spaced doses of the polypeptide, but prompt and intense for high doses. Long-lasting hypotension was obtained by intravenous infusion of bombesin, but repeated infusions caused tachyphylaxis. Bombesin-induced hypotension was not affected by pretreatment with atropine.6. Bombesin may be easily distinguished from all other known peptides active on vascular and extravascular smooth muscle by its effects on blood pressure. This does not apply to bombesin-like peptides, such as alytesin and ranatensin.

Angiotensin II↗

[Lamotrigine in the therapy of resistant epilepsy].

OBJECTIVE: To evaluate the efficacy of lamotrigine as single agent in patients with refractory epilepsy. MATERIALS AND METHODS: Forty-seven adult patients with refractory epilepsy, in the initial phase received carbamazepine (1208 +/- 82.9 mg/day) plus lamotrigine (561.7 +/- 76.8 mg/day); during the second phase they received lamotrigine alone (206.4 +/- 44.4 mg/day). RESULTS: Lamotrigine monotherapy significantly improved the number of seizures per week in comparison to lamotrigine combined with carbamazepine (p < 0.0001). CONCLUSIONS: Lamotrigine as single agent is more effective than carbamazepine + lamotrigine in patients with refractory epilepsy.

Adolescent↗

[Efficacy of vigabatrin associated with carbamazepine in the treatment of epilepsy. Follow up 1993-1996].

PURPOSE: To verify tolerance and clinical efficacy of vigabatrin (VGB), a new antiepileptic drug, in an add-on therapy with carbamazepine (CBZ). PATIENTS AND METHODS: From september 1993 to december 1996, 35 patients with partial complex seizures (CPC) and CPC plus secondary generalization were treated, with VGB plus CBZ, VGB dose was 1.41 +/- 0.26 (g/die +/- SD) and CBZ 2.28 +/- 0.60 (g/die +/- SD). RESULTS: Patients were followed-up every 4 months showing an improvement between 61.5% and 68.8% from baseline. CONCLUSIONS: In all patients we observed an improvement during the follow-up period. Side effects were mild and well tolerated.

Adult↗