L.G. Micossi

Antidipsogenic effect of intracranial injections of substance P in rats.

1. The effect on water intake of intracranial injections of Substance P was studied in the rat. 2. Substance P strongly inhibited drinking elicited by Angiotensin II, Carbachol water deprivation or sodium chloride load, in that order. 3. The peptide was particularly effective when water intake was induced by injections of Angiotensin II into the preoptic area. In these experiments, drinking was inhibited by doses of Substance P as low as 1 ng. 4. The results suggest that in the rat Substance P may play a role in the brain in the regulation of water intake, acting as a thirst inhibitor.

Antidipsogenic effect of intraventricular administration of eledoisin to rats

Summary Intracerebroventricular injections of eledoisin produced a dose dependent inhibition of water intake caused by intraventricular administration of angiotensin or carbachol, water deprivation or sodium chloride load. The peptide appeared particularly effective in rats treated with carbachol or deprived of water (threshold dose, 0.01 μg/rat), while in animals loaded with sodium chloride it was effective only if administered in large doses (20 μg/rat). Eledoisin did not affect food intake. The results of the experiments suggested that brain factors may play a role in the regulation of water intake. One of these factors could be Substance P, the endecapeptide of mammalian brain and gut, which is chemically related to eledoisin and shares with it pratically the same pharmacological spectrum.

Suppression of drinking but not feeding by central eledoisin and physalaemin in the rat

The tachykinins, eledoisin and physalaemin, given by intracerebroventricular (i.c.v.) injection have been shown to be potent antidipsogenic agents in rats. To evaluate their selectivity of action on rat ingestive behaviors, we compared their effects following i.c.v. injection on the intake of water, of milk containing 3.5 or 15% fat, and of solid food. The two tachykinins inhibited water intake induced by i.c.v. angiotensin II or by cellular dehydration, but did not reduce the intake of 15% fat milk or of solid food. The intake of 3.5% fat milk was inhibited only by the highest dose (1000 ng/rat) of eledoisin which also increased grooming and locomotion. The present findings suggest that in adult rats central eledoisin and physalaemin exert a selective suppressive effect on drinking behavior without affecting feeding.

Dipsogenic effect of angiotensin II, bombesin and tachykinins in the duck

The effect on drinking behaviour of intracerebroventricular injections of angiotensin II, bombesin, eledoisin and substance P was studied in the duck. While substance P was almost completely ineffective, angiotensin II, bombesin and eledoisin elicited a clear dipsogenic response which was dose-dependent and apparently specific. Angiotensin II was about 10 times more potent than bombesin and far more potent than eledoisin. These results confirm once more the wide phylogenetic distribution of the dipsogenic response to angiotensin II. Furthermore, they show that bombesin and eledoisin, which potently inhibit water intake in the rat, exert in the duck a dipsogenic effect strictly parallel to that elicited in the pigeon. On the basis of the animal species so far tested it is possible to hypothesize that bombesin and tachykinins stimulate water intake in birds, while inhibiting drinking in mammals.

Modifications of drinking behaviour and of arterial blood pressure induced by tachykinins in rats and pigeons

Intracerebroventricular injections of the naturally occurring tachykinins eledoisin, physalaemin and substance P elicit a powerful antidipsogenic effect in the rat, while in the pigeon they potently stimulate water intake. The aim of this paper was to study in conscious rats and pigeons the vascular effect of these peptides and to compare this effect to the one elicited on water intake.The results of these experiments demonstrate that there is no direct relationship between the two effects.Our findings suggest that the effect of these peptides on water intake might be specific on CNS and not related to their vascular activity.

Physalaemin, a new potent antidipsogen in the rat

Abstract In this paper the effect on water intake of intracerebroventricular administration of the naturally occurring endecapeptide physalaemin is reported. Drinking was induced by intracerebroventricular injection of angiotensin II (100 ng/rat) or carbachol (300 ng/rat), water deprivation or NaCl load. Physalaemin produced a dose-dependent inhibition of water intake induced by angiotensin II. The inhibition was virtually complete at the dose of 500 ng/rat. The minimum dose employed (50 ng/rat) produced a 6% drinking inhibition. Physalaemin inhibited drinking induced by carbachol. The threshold dose was 125 ng rat . A virtually complete inhibition was produced by physalaemin, 1μg. The effect was dose-dependent. In water deprived rats 10 μg, but not lower doses, of the peptide produced a significant inhibition of water intake. The effect was short-lasting and ceased 30 min after the injection. Physalaemin was completely ineffective in sodium chloride-loaded rats, in spite of the very large doses employed (up to 5 mg/rat). The results of these experiments demonstrate that physalaemin is a potent antidipsogenic agent, but do not allow any conclusion to be made about the mechanism of its inhibitory effect. However, it is reasonable to propose that the effect is specific to the CNS and not simply due to the very marked vascular activity of the peptide.

Bombesin potently stimulates water intake in the pigeon

Abstract Bombesin, injected intracerebroventricularly, evoked a potent dipsogenic response in the pigeon. The effect was dose-dependent and apparently specific since no other behavioural alteration was ever observed. The findings suggest that endogenous bombesin-like peptides may be involved in the control of water intake in the pigeon.

Drinking and feeding inhibition by ICV pulse injection or infusion of bombesin, ranatensin and litorin to rats.

The effects on ingestive behavior of the naturally occurring bombesin-like peptides ranatensin and litorin were studied in comparison to those of bombesin by intracerebroventricular pulse injection or by continuous infusion in the rat. Ranatensin and litorin, like bombesin, proved to inhibit drinking and feeding behavior. Marked differences, however, were observed in their effects. In particular our results indicate that these peptides possess different selectivity of action on drinking elicited by different dipsogenic stimuli and different potency and effectiveness in inhibiting food intake induced by food deprivation. Moreover, the effects of the three peptides were markedly affected also by the modality of administration (pulse injection or continuous infusion). On the basis of these results it seems possible to hypothesize that the endogenous bombesin-like peptides may differently affect rat ingestive behavior according to their structure and to the rate and modality of their release in the brain.

Angiotensin II antagonists versus drinking induced by bombesin or eledoisin in pigeons

Abstract The angiotensin II analogues Sar 1 ,Ile 8 -,Sar 1 ,Leu 8 - and, to a lesser extent, Sar 1 ,Ala 8 - and Sar 1 -Gly 8 -angiotensin II proved to inhibit angiotensin-induced drinking in the pigeon, but did not significantly affect drinking induced by eledoisin or bombesin. The results suggest that the dipsogenic response elicited by bombesin or eledoisin, although almost identical to that evoked by angiotensin II, is mediated by the activation of central receptors different from those of angiotensin-induced drinking. These findings are consistent with the hypothesis that several peptidergic mechanisms are involved in the regulation of water intake.

Effect of bombesin on drinking induced by angiotensin II, Carbachol and water deprivation in the rat

Summary Bombesin, injected by intracerebroventricular route to rats, inhibits drinking induced by angiotensin II, carbachol or water deprivation. The effect is apparently specific and not due, or at least only in part related, to other specific or non specific behavioural alterations.