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Biomedical subjects

F Guidobono

Publications and source records attributed to F Guidobono.

14 recordsLinked to original sources
PubMed1992

The short term effect of peripherally administered brain-gut peptides on gastric acid secretion in rats.

Certain brain gut-peptides are known to either stimulate or inhibit gastric acid secretion in several species after direct injection into the central nervous system. However there is inconsistency of published results on the gastric acid secretory response to some of these peptides after peripheral administration in different experimental systems. Seven peptides, namely neurotensin (NT), substance P, cholecystokinin (CCK), thyrotropin releasing hormone (TRH), human calcitonin (hCT), rat calcitonin-gene-related peptide (rCGRP) and bombesin, all known to modulate gastric acid secretion after central administration, were initially screened for activity after peripheral (subcutaneous) injection of 10 micrograms/kg body weight in a single rat model. Peptides showing an effect were retested at lower doses. Despite the inherent variability of the gastric acid secretory response in the non-anaesthetized pylorus ligated rat, a standardized experimental design confirmed that reproducible and statistically valid results could be obtained. The technical feasibility of using a one hour collection period as might be appropriate for short acting peptides was demonstrated by the significant dose dependent inhibitory activity of salmon calcitonin. In this model, NT and substance P had no significant effect on either volume or concentration of acid secreted, CCK showed a slight stimulation of acid output, and TRH, hCT, rCGRP and bombesin all inhibited acid output; CGRP and bombesin were active at 10 and 100-fold lower doses. The potent and inhibitory activity of bombesin in this system is in disagreement with other publications reporting no effect or variable stimulatory effect in rats. Time and dose dependent responses in our rat system indicate that this apparent discrepancy may be explained by the short duration of action of bombesin.

Animals↗
PubMed1992

Decrease in rat brain calcitonin binding sites and adenylyl-cyclase activity during ageing.

In order to investigate the effects of ageing on the cerebral receptors for calcitonin (CT), we used an in vitro autoradiographic method to study the distribution of the binding sites for eel CT (eCT) in young and old rat brain. The inhibitory action of eCT on adenylyl-cyclase (AC) activity upon isolated brain cell membranes was also evaluated. The results show area-specific reduction of binding particularly in the hypothalamus and pons medulla of the old rat. The inhibitory action of eCT on AC activity was significantly reduced in the same areas, whereas in the striatum and mesencephalon no changes were observed. The parallel decrease of binding of eCT and of the inhibitory action of eCT on AC in ageing may represent a functional decline of neuronal activities during ageing.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Effects of selective histamine H3-receptor ligands on prolactin and growth hormone secretion in the rat.

The effects of intracarotid (i.a.) administration of the histamine (HA) H3-receptor agonist (R)-alpha-methyl-histamine (alpha MeHA) and of the H3-antagonist thioperamide, (THIO) on basal or morphine (M)-induced prolactin (PRL) and growth hormone (GH) secretion were studied in male rats. M was administered 3 h after the H3-drugs. Neither THIO (2.5 mg/kg) nor alpha MeHA (10 mg/kg) changed basal PRL levels and only THIO enhanced the PRL-releasing effect of M (6 mg/kg). Basal GH secretion was not modified by THIO. alpha MeHA slightly increased GH secretion. THIO significantly decreased M-stimulated GH secretion (1 mg/kg, i.a.) and alpha MeHA slightly increased it. These results, in agreement with previous evidence obtained after central HA administration, indicated that endogenous brain HA facilitates PRL and inhibits GH secretion.

Animals↗
PubMed1991

Antinociceptive activity of eel calcitonin, injected into the inflamed paw in rats.

This study examined the possible peripheral activity of eel calcitonin in the modulation of the response to noxious pressure on inflamed paws in rats (Randall and Selitto test). The intraplantar injection of eel calcitonin (20-200 ng/rat) but not the subcutaneous administration (200 ng and 2 micrograms/rat, s.c.), was able to significantly inhibit hyperalgesia induced by intraplantar injection of carrageenin. The development of oedema on the other hand was not inhibited. The intraplantar administration of eel calcitonin (200 ng/rat) in a non-inflamed paw did not modify paw pressure thresholds. Eel calcitonin (200 ng/rat, intraplantar, i.pl.) was also able to elicit an antinociceptive effect on formalin-induced hyperalgesia, both when the peptide was injected before or after (60 min) formalin. This effect, at difference with morphine (80 micrograms/rat, i.pl.), was not blocked by naloxone (10 micrograms/rat, i.pl.). These results demonstrate the local antinociceptive effect of eel calcitonin in inflammatory pain and might indicate a new way of using calcitonin in the control of pain.

Analgesics↗
PubMed1991

Stress-related changes in calcitonin gene-related peptide binding sites in the cat central nervous system.

The possibility of area-specific changes in binding sites for CGRP in response to stress was studied in cat CNS after repeated sleep-deprivation and restriction of movement. Brain sections were obtained from a cat placed under stressful conditions for 2 h the 1st day, 6 h the 2nd day and 24 h the 3rd day. Changes in CGRP binding sites were evaluated by an in vitro autoradiographic technique with 125I-Tyr-rat-CGRP as a ligand. The autoradiograms were then compared with those of control animals. The results show decreased labelling in the cortex prefrontalis and pyriformis and in some basal ganglia (n. caudatus, claustrum, n. entopedencularis). Increased CGRP binding site densities were seen in areas involved in the integration of sensory information, in the control of endocrine secretion and in those that participate in sleep-walking cycles. These changes in CGRP binding in selective CNS areas following stress suggests that CGRP plays a role in processes of adaptation.

Animals↗
PubMed1991

Effect of unmodified eel calcitonin on gastric acid secretion and gastric ulcers in the rat.

A new peptide, eel calcitonin (eCT), synthesized to the sequence of calcitonin (CT) extracted from the ultimo branchial bodies of eels, is now on the market in some countries for clinical use in the treatment of Paget's disease of bone and in the prophylaxis or treatment of certain osteoporoses. We have now studied the effect of eCT on the inhibition of gastric acid secretion and protection against experimentally induced gastric ulcers in rats as other CTs have previously been shown to have such effects. EelCT shows a dose dependent inhibition of gastric acid secretion, both volume and concentration of acid - dose range 100-900 ng/Kg injected subcutaneously. Central administration is also effective at a dose of 100 ng/rat. There is no published evidence for a direct effect of CTs in the stomach and there is considerable speculation on possible mediating pathways. Somatostatin may be involved in the inhibitory effect of eCT on gastric acid secretion because when administered both centrally or peripherally eCT is ineffective in rats depleted of somatostatin by pretreatment with cysteamine. However, other mechanisms must also be involved as eCT has no preventive effect against gastric ulcers induced by ethanol but has a high index of protection against ulcers induced by cold restraint stress or indomethacin.

Animals↗
PubMed1990

A selective role for brain histamine in prolactin release induced by opiates.

We studied the effects of histamine (HA) antagonists on the facilitatory action of morphine (M) and beta-endorphin (beta E) on prolactin (PRL) release and the effect of alpha-fluoromethylhistidine (alpha-FMH, inhibitor of HA synthesis) on beta E-induced PRL secretion. Male rats were injected intracerebroventricularly (i.c.v.) with mepyramine (MEP, H1-antagonist, 0.8 mumol/rat) or ranitidine (RAN, H2-antagonist, 0.4 mumol/rat) 10 min before M (6 mg/kg, intracarotid, i.a.) or beta E (0.25 micrograms/rat, i.c.v.). alpha-FMH (200 micrograms/rat, i.c.v.) was administered 3 h before beta E. Plasma PRL levels were measured at various times before and after drug treatment. RAN but not MEP significantly reduced PRL release induced by M whereas neither HA-antagonists nor alpha-FMH modified beta E-induced PRL release. The results obtained show that brain HA contributes through activation of H2-receptors to the PRL facilitatory action of M but not of beta E.

Animals↗
PubMed1990

Inhibitory effects of centrally administered /ASU1-7/eel calcitonin on basal and stimulated prolactin release in rats.

We investigated the effects of /ASU1-7/eel calcitonin (ASU1-7eelCT) on basal and stimulated prolactin (PRL) release in male rats. /ASU1-7/eelCT was administered intracerebroventricularly (icv) into freely moving rats with indwelling catheters. The administration of /ASU1-7/eelCT (2.5 micrograms/rat, icv) significantly inhibited basal PRL secretion. When PRL secretion was stimulated by exposing rats to restraint stress, /ASU1-7/eelCT (250 ng; 800 ng; 2.5 micrograms/rat, icv) dose-relatedly inhibited the PRL surges at 10 min after stress. The same doses of icv /ASU1-7/eelCT were effective in inhibiting morphine (6 mg/kg, intracarotid, ia-induced PRL release. No effect on stress-induced PRL secretion was observed when the peptide was administered intracarotid at the dose of 10 micrograms/rat. These results demonstrate that /ASU1-7/eelCT, as we previously observed with salmon calcitonin (sCT), has central inhibitory activity on PRL secretion, probably through enhancement of hypothalamic inhibitory pathways involved in the control of PRL.

Analysis of Variance↗
PubMed1989

Effects of age on binding sites for calcitonin gene-related peptide in the rat central nervous system.

The binding site distribution of calcitonin gene-related peptide (CGRP) was studied in the central nervous system of aged rats (22 months old) and compared with that of young rats (2 months). The regional distribution of [125I]Tyr-rat CGRP binding in coronal sections of young and old rat CNS was examined by an in vitro autoradiographic technique. The results, showed that in aged rats there was a marked reduction in CGRP binding, without any change in binding affinity, in the hippocampus, the nucleus rhomboideus, the nucleus arcuatus, the colliculus superior, the substantia grisea centralis and the spinal cord. In the cortical areas, the amygdala, the caudatus putamen and the accumbens binding was not modified. In the cortex cerebellaris CGRP binding was strikingly greater in the aged rats. The increase in binding might be a consequence of an adaptive process due to a decline of the peptide synthesis with age and is suggestive of a role for CGRP in the cerebellum functions.

Aging↗
PubMedDate not supplied

Treatment with pertussis toxin does not prevent central effects of eel calcitonin.

To determine whether or not the CNS inhibitory activity of eel calcitonin (eCT) on adenylyl cyclase is the endocellular mechanism underlying the antinociceptive effect of the peptide, as shown for morphine analgesia, we administered Bordetella pertussis toxin (PTX) by intracerebroventricular (ICV) injection (0.5 microgram/rat) to block the receptor-mediated inhibition of adenylyl cyclase. In PTX-treated rats there was no change in eCT (2.5 micrograms/rat, ICV)-induced antinociceptive activity (hot-plate test) nor in eCT (100 ng/rat, ICV) inhibition of gastric acid secretion (Shay test) whereas morphine (5 micrograms/rat, ICV) analgesia was significantly reduced. In vitro studies showed no reduction of eCT binding in the CNS of rats treated with PTX in vivo. Moreover, PTX treatment did not change the inhibitory effect of eCT on adenylyl cyclase in isolated membranes from rat striatum in contrast with opiates (DAME and morphine) whose effects were lost. As PTX is known to inactivate the guanidine binding inhibitory protein Gi, these data suggest that a G protein, distinct from the Gi protein involved in the coupling of opiate receptors into a functional response, could be responsible for regulating the intracellular pathways resulting in eCT-induced antinociceptive effect and inhibition of gastric acid secretion.

Adenylate Cyclase Toxin↗
PubMedDate not supplied

Specific inhibition of basal gastric acid secretion by salmon calcitonin in rats does not necessarily involve a central pathway.

It is well established that salmon calcitonin (sCT), given either by central (intracerebroventricular) or peripheral (parenteral) injection is a potent inhibitor of gastric acid secretion. It is generally believed that this effect of sCT is mediated by the central nervous system based on reports that the effective peripheral dose is up to 1000 times greater than the effective dose administered centrally. We have reexamined this hypothesis by carrying out a number of independent experiments in two laboratories on the effect of sCT, given either by intracerebroventricular or by subcutaneous injection, on basal gastric acid secretion in unanaesthetized rats. Statistical evaluation of the data showed the reproducibility of the effective inhibitory dose ranges of sCT despite the inherent variability of the pylorus ligated rat system (Shay test). The effective dose range for sCT given centrally was between three- and ten-fold lower than that for peripherally administered sCT. There is no published evidence that a significant amount of peripherally administered sCT passes through the blood-brain barrier to relevant areas of the brain and this is confirmed in our study by autoradiography of serial sections of brain following intravenous administration of radioiodinated sCT. It therefore appears that the inhibitory effect of sCT, given centrally or peripherally, may not necessarily be mediated by a common pathway in the central nervous system. Our results also show that the inhibitory effect of peripherally administered sCT is lost when rats are treated with cysteamine to deplete somatostatin, thus implicating somatostatin as a peripheral mediator.

Analysis of Variance↗