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Biomedical subjects

M Massi

Publications and source records attributed to M Massi.

At least 91 records · Page 5Linked to original sources
PubMed1990

Angiotensin/aldosterone synergy governs the salt appetite of the pigeon.

Sodium-replete pigeons drink excess 3% NaCl following concurrent treatment with both i.m. deoxycorticosterone acetate and pulse i.c.v. (p.i.c.v.) angiotensin II. This is not just a consequence of the water intake induced by p.i.c.v. angiotensin II, since the tachykinin eledoisin, given at equidipsogenic dose, does not evoke intake of salt. On the other hand, salt intake is not aroused in the sodium replete pigeon by continuous i.c.v. (c.i.c.v.) infusion of hyperosmotic mannitol (0.7 M) and c.i.c.v. infusions of hyperosmotic NaCl (0.3 M) or mannitol have no effect on the salt intake of the sodium deplete pigeon, or have effects that are unrelated to brain sodium. The salt appetite of the pigeon, like that of the rat, is evoked by an angiotensin and aldosterone synergy, and the angiotensin/aldosterone mechanism may be the general vertebrate theme of this behavior.

Aldosterone↗
PubMed1989

Vasopressin release induced by intracranial injection of tachykinins is due to activation of central neurokinin-3 receptors.

The present study investigated the effect on vasopressin release of the intracerebroventricular injection of tachykinins in rats. The selective neurokinin (NK)-3 receptor agonists [MePhe7]neurokinin B and [Asp5,6MePhe8]substance P(5-11) evoked vasopressin release. Also eledoisin, physalaemin and kassinin, which show good affinity for central NK-3 receptors, released vasopressin. On the other hand, neurokinin A, substance P and the selective NK-1 agonist [Pro9,Met(O2)11]substance P were devoid of activity. At doses releasing vasopressin, central injection of NK-3 selective agonists and of the natural tachykinins never produced hypotension. Present results indicate that activation of central NK-3 receptors is involved in vasopressin release induced by tachykinins, and rule out the possibility that the effect might be consequent to hypotension due to passage of tachykinins into the peripheral circulation.

Animals↗
PubMed1989

Methoctramine, a selective M2 alpha muscarinic receptor antagonist, does not inhibit carbachol-induced drinking in the rat.

Methoctramine, a selective M2 alpha muscarinic receptor antagonist, was examined for its ability to inhibit carbachol-induced drinking in the rat. Intracerebroventricularly (i.c.v.) administered methoctramine was devoid of activity up to a dose of 100 nmol/rat, whereas higher doses were toxic under our experimental conditions. 4-DAMP, pirenzepine and hexahydrosiladifenidol were also tested. The rank potency order for the compounds (4-DAMP greater than pirenzepine = hexahydrosiladifenidol) was similar to that for their affinity at M1 receptors, as found in experiments in vitro. The putative M1 agonist McN-A-343 was inactive up to doses of 13.9 micrograms/rat. Our data suggest that M2 alpha receptors do not mediate cholinergic drinking in the rat. The question whether M1 or M2 beta muscarinic receptors are involved in this response still awaits a firm answer.

Angiotensin II↗
PubMed1989

Suppression of salt intake in the rat by neurokinin A: comparison with the effect of kassinin.

The present study investigates the effect of the mammalian tachykinin neurokinin A on salt intake in the rat. Intracerebroventricular injection of neurokinin A inhibited salt intake elicited by sodium depletion, by subchronic deoxycorticosterone treatment and by adrenalectomy. It also inhibited the need-free salt intake of female rats that had been previously depleted of sodium. Since different brain mechanisms elicit salt intake in these experimental models, it is concluded that neurokinin A exerts a general antinatriorexic effect. Apparently, its inhibitory effect on salt intake is not due to malaise or competing behaviors, as shown by the fact that the doses of neurokinin A which suppress salt intake do not suppress milk intake. In comparison to the amphibian tachykinin kassinin, neurokinin A possesses a similar spectrum of antinatriorexic activities, but is markedly less potent and less effective in all the experimental models investigated. These findings suggest that activation of neurokinin A receptors cannot solely account for the potent antinatriorexic effect of kassinin and of other nonmammalian tachykinins.

Adrenalectomy↗
PubMed1989

Structure-activity relationships in prazosin-related compounds. Effect of replacing a piperazine ring with an alkanediamine moiety on alpha 1-adrenoreceptor blocking activity.

Several prazosin-related compounds were synthesized in which the piperazine ring of prazosin (1) was replaced by an alkanediamine chain and were evaluated for their blocking activity on alpha 1- and alpha 2-adrenoreceptors in isolated rat vas deferens. All the compounds investigated proved highly selective toward the alpha 1-adrenoreceptor owing to a very low affinity for alpha 2-adrenoreceptors. Furthermore, compounds 2, 9, and 13 were also investigated in vivo to determine their hypotensive effect on anesthetized rats, which were compared with that of prazosin (1). It was confirmed that the piperazine moiety of 1 is not essential for potency. However, optimum activity depends on two parameters: carbon-chain length of the alkanediamine moiety and N-methylation of both the amide and the 2-amino functions. In the desmethyl series, optimum activity was associated with the lower homologues (2-4) bearing a chain of two to four methylenes whereas in the N,N'-dimethyl series peak potency was observed with a six-carbon chain as in 13. Compound 13 proved the most active of the series and was more potent than prazosin (1) in both in vivo and in vitro assays. It is hypothesized that the alpha 1-adrenoreceptor incorporates a lipophilic area that is located between the binding sites for the quinazoline and the furoyl moieties and is able to accommodate a polymethylene chain.

Adrenergic alpha-Antagonists↗
PubMed1989

Label distribution after injection of labelled tachykinins into the rat lateral cerebroventricle.

The present study investigated the label distribution in several brain regions, as well as in the peripheral circulation, following injection of labelled tachykinins [( 3H]-substance P, [3H]-eledoisin or [125I]-neurokinin A) into the lateral cerebroventricle of the rat. A widespread label distribution, extending as far as to the brainstem, was detected. Hypothalamus, striatum and hippocampus were the most labelled regions by the 3 labels; however the patterns of distribution of the 3 labelled tachykinins showed marked differences. Distribution in the brain was rapid, reaching a maximum usually within 2 min after injection and declining slightly afterwards. Large amounts of label (1/6-1/15 of the total amount injected) were detected in serum even at 2 min after injection and increased thereafter, reaching a maximum at 10-15 min.

Animals↗
PubMed1988

The tachykinin NH2-senktide, a selective neurokinin B receptor agonist, is a very potent inhibitor of salt appetite in the rat.

The tachykinin peptide [Asp5.6, MePhe8]substance P(5-11) (NH2-senktide), a senktide analogue lacking the N-terminal succinyl group, is a selective and metabolically stable NK-3 receptor agonist. In the present study it potently inhibited salt appetite induced by sodium depletion in rats. Argo-neurokinin B, too, inhibited salt appetite, but was less potent than NH2-senktide. Neither peptide inhibited drinking behaviour induced by subcutaneous hypertonic NaCl. NH2-senktide slightly inhibited angiotensin-induced drinking, while Argo-neurokinin B was ineffective. On the other hand, eledoisin was a potent inhibitor in the 3 behavioural tests. Present results indicate that activation of NK-3 receptors is involved in the antinatriorexic action of tachykinins, and that different receptor subtypes might be involved in the different effects of tachykinins on the rat ingestive behaviour.

Animals↗
PubMed1988

Inhibitory effect of kassinin on salt intake induced by different natriorexigenic treatments in the rat.

Pulse intracerebroventricular (i.c.v.) injection of kassinin, 100-500 ng/rat, potently inhibits salt intake induced by sodium depletion. The effect appears to be selective since the same doses of kassinin do not inhibit milk intake or solid food intake. When given by continuous i.c.v. infusion kassinin elicits a clear anti-natriorexic effect at doses of 1-10 ng/min/rat. Kassinin not only suppresses sodium depletion-induced salt appetite, but it also inhibits sodium intake induced by pulse i.c.v. injection of renin or by subcutaneous (s.c.) deoxycorticosterone. Finally it also suppresses the elevated need-free intake of 1.5% NaCl in multidepleted female rats, which is not mediated by the renin-angiotensin-aldosterone system. These findings show that kassinin exerts a general suppressive effect on salt intake, irrespective of the natriorexigenic treatment. The present study suggests that the kassinin-like peptides that are endogenous to the rat brain may be involved in the behavioral regulation of extracellular body fluids in the rat by inhibiting sodium intake.

Animals↗
PubMed1988

Neurokinin A selectively inhibits water intake in the rat.

The results of the present study show that the intracerebroventricular injection of neurokinin A elicited a selective antidipsogenic effect in the rat. Neurokinin A proved to be an extremely potent inhibitor of drinking elicited by subcutaneous administration of hypertonic NaCl, and produced also a statistically-significant inhibition of food-associated drinking. On the other hand, it did not affect drinking evoked by other dipsogenic determinants, such as water deprivation and intracerebroventricular injection of carbachol or of angiotensin II. Thus, neurokinin A shows a spectrum of antidipsogenic activity clearly different from that of substance P, the other mammalian tachykinin so far tested on drinking behaviour in the rat, which appears to be a non-selective antidipsogenic agent. The findings of the present study suggest that different tachykinins, endogenous to the brain of the rat, might subserve distinct roles in the control of drinking behaviour.

Angiotensin II↗
PubMed1988

Inhibitory effect of intracranial injections of tachykinins on angiotensin-induced drinking in the cat.

The tachykinins eledoisin, substance P and kassinin were administered by pulse intracerebroventricular (ICV) injections to cats made thirsty by ICV angiotensin II, 100 ng per cat. Eledoisin, 100 ng per cat, produced an inhibition of drinking which was larger (56.0 vs. 45.2%) and lasted longer than that evoked by 400 ng per cat of substance P. Kassinin, 100 ng per cat, did not evoke any effect at all. The treatment with these peptides neither produced signs of discomfort nor induced any other behavioural alteration. The results of present experiments suggest that the antidipsogenic effect of tachykinins is a phenomenon of general interest among mammals.

Angiotensin II↗
PubMed1988

Vasopressin release induced by intracranial injection of eledoisin is mediated by central angiotensin II.

Pulse intracerebroventricular injection of eledoisin, but not of substance P, markedly increases plasma vasopressin levels in the rat. Intracerebroventricular pretreatment with sarcosine1, alanine8-angiotensin II, 1 microgram/rat, completely suppresses the effect of eledoisin, suggesting that it is mediated by angiotensin release and angiotensin II receptor activation. The vasopressin releasing effect of eledoisin is neither due to peripheral haemodynamic alterations, nor to activation of the peripheral renin-angiotensin system. It is apparently related to central angiotensin release in a specific neuronal pathway subserving vasopressin release. This effect is not secondary to inhibition by tachykinins of the brain mechanisms for angiotensin-induced drinking, but is probably expression of direct activation of specific tachykinin receptors controlling vasopressin release.

Angiotensin II↗
PubMed1987

The apparent dependence of salt appetite in the pigeon on endogenous angiotensin II.

Blockade of endogenous angiotensin II (ANG II) biosynthesis by intramuscular administration of the angiotensin converting enzyme inhibitor captopril (1 or 10 mg/kg b.w.t.) completely suppressed salt appetite induced by sodium depletion in the pigeon. The effect was selective since captopril did not reduce deoxycorticosterone (DOCA)-induced salt appetite nor water drinking to ANG II and eledoisin. Blockade of brain ANG II receptors by pulse intracerebroventricular (pICV) injection of the ANG II receptor antagonist [Sarcosine1, isoleucine8] ANG II produced a marked, although partial, inhibition of salt appetite. The inhibition was quantitatively similar to the effectiveness of the ANG II receptor blockade, as measured by the suppression of drinking to pICV ANG II. Blockade of brain aldosterone (ALDO) receptors by pICV injections of the mineralocorticoid receptor antagonist RU-28318 did not significantly suppress depletion-induced appetite at doses that markedly reduced DOCA-induced salt appetite. These findings suggest that the pigeon might be completely dependent on ANG II for the expression of depletion-induced salt appetite. This is in contrast with what has been found in the rat, in which blockade of both ANG II and ALDO are necessary to suppress the appetite.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1987

Effect of the 5HT2 antagonist ritanserin on food intake and on 5HT-induced anorexia in the rat.

The present study investigated the effect on the rat's eating behavior of the new selective 5HT2 antagonist ritanserin. The results obtained indicate that: single subcutaneous (SC) injection of ritanserin, at doses between 0.1 and 1 mg/kg b.wt., neither elicits food intake in sated rats, nor increases the intake induced by food deprivation; subchronic SC treatment (15 days) with 0.1 mg/kg does not increase food intake nor body weight gain; subchronic SC treatment with high doses, 1 or 10 mg/kg, produces small and transient increases in food intake without affecting body weight gain. When ritanserin was tested for its ability to block the anorectic effect of exogenous 5HT, it inhibited the effect of intraperitoneal (IP) 5HT, but proved to be completely inactive versus the effect of 5HT injected into the hypothalamic paraventricular nucleus, which is highly sensitive to this effect of 5HT. This last finding suggests that the anorectic action of central endogenous 5HT is also not blocked by ritanserin, thus proposing a reasonable explanation for the absence of orexigenic effect following its administration. Moreover, it suggests that in rats the hypothalamic receptors mediating the effect of 5HT on eating behavior are different from the 5HT2 of the frontal cortex which have been shown to be completely blocked by ritanserin under the experimental conditions employed in our study.

Animals↗
PubMed1987

Effect of kassinin, neurokinin A and neurokinin B on drinking behaviour in the pigeon.

Intracerebroventricular (i.c.v.) injection of kassinin produced a prompt and copious drinking response at doses of 10-1000 ng/pigeon, in the absence of other behavioural alterations or of changes in core temperature. Neurokinin A and B evoked drinking, but they were respectively 10 and 100 times less potent than kassinin. Intraperitoneal injection of kassinin elicited drinking, but at doses about 1000 X larger than the i.c.v. ones. The angiotensin antagonist [Sar1, Leu8]angiotensin II did not reduce drinking induced by i.c.v. kassinin, suggesting that its effect is not due to interaction with the central renin-angiotensin system. Moreover, the effect is apparently independent of the mechanisms controlling hypovolaemic and hyperosmotic thirst since exact additivity was found in the dipsogenic response when i.c.v. kassinin was administered in the presence of a hypovolaemic (subcutaneous (s.c.), polyethylene glycol) or hyperosmotic (s.c. hypertonic NaCl) dipsogenic stimulus. The present findings show that kassinin, neurokinin A and B share with the tachykinins already tested (eledoisin, physalaemin, substance P) a common dipsogenic action in pigeons. However, marked differences exist in their dipsogenic potency. This order of potency, eledoisin = kassinin = physalaemin greater than neurokinin A = substance P greater than neurokinin B, is not consistent with the tachykinin receptor subtypes so far proposed.

Angiotensin II↗
PubMed1987

Salt appetite in the pigeon in response to pharmacological treatments.

1. In response to furosemide-induced sodium depletion pigeons showed a robust salt appetite. Following the 1st depletion they started to ingest 3% NaCl after a latency of 373 +/- 69 s and in 24 h they took 21.16 +/- 3.07 ml of this solution (vs. a daily mean intake of 1-2 ml prior to the depletion). 2. The appetite was selective as shown by the fact that when, after depletion, 0.34 M-CaCl2 was offered (which is equiosmotic to 3% NaCl) pigeons took just a trivial amount of it. 3. Analysis of sodium losses following the natriuretic treatment revealed that pigeons respond to sodium depletion with an excessive overconsumption of NaCl solution. In the 2 h after access to salt they took about 3 times the amount of sodium lost. 4. Repeated sodium depletions sharply reduced the latency to the ingestion of salt and produced larger intakes. However, the overall amount of salt taken in 24 h after the later depletions was very similar and statistically indistinguishable from that taken following the 1st depletion. 5. Subchronic deoxycorticosterone acetate treatment (2 mg pigeon-1 day-1 I.M.) increased daily 3% NaCl intake, but large variability was observed in the response. 4 mg pigeon-1 day-1 evoked a reliable 3% NaCl intake which was particularly marked from the 5th day of the treatment. 6. Pulse intracerebroventricular (I.C.V.) injection of purified hog renin evoked water intake within about 1 min of injection, followed (about 6 h later) by increased salt intake. In the 24 h after renin injection pigeons took 16.58 +/- 2.89 ml of 3% NaCl. On the 2nd day following injection salt intake was still higher than in controls. 7. In conclusion, our results show that pigeons respond to sodium depletion with a robust salt appetite. Moreover, salt appetite can be evoked by deoxycorticosterone acetate as well as by renin. These findings suggest that in the pigeon salt appetite may be an endocrine-induced behaviour controlled by mineralocorticoids and by the renin-angiotensin system.

Animals↗
PubMed1986

The role of the subfornical organ in the drinking behavior of the pigeon.

Pigeons with radiofrequency lesions that damaged the subfornical organ (SFO) (n = 4) or that isolated it from adjacent structures (n = 5), but not sham-lesioned pigeons, were unresponsive to blood-borne (i.p.) ANG II (100 micrograms/pigeon) in the immediate postoperative period and for 60 days thereafter. These animals were less sensitive to hypovolemic challenge (20% PEG), but they responded normally to 24 h of water deprivation and to cellular dehydration. Despite their unresponsiveness to bloodborne ANG II, the lesioned pigeons drank normally to 10 ng of i.c.v. ANG II given as early as 10 days after surgery, and they drank reliably and vigorously but less in total volume to 100 ng i.c.v. They also drank quickly, vigorously, and in normal total volume to i.c.v. tachykinins and bombesins, and to the peripheral (i.p.) bombesins. Peripheral (i.m.) tachykinins produced only low volume and variable drinking in all birds tested regardless of brain damage. The SFO of the pigeon, like that of the mammal, is essential for drinking evoked by blood-borne ANG II and is not necessary for thirst aroused by ANG II acting from within the cerebral ventricles. Lastly, it does not mediate the dipsogenic effects of the tachykinins or the bombesins.

Angiotensin II↗