A. Prato

Amylin given by central or peripheral routes decreases gastric emptying and intestinal transit in the rat

The effect of rat amylin on gastric emptying and intestinal transit in the rat was examined. Amylin administered intracerebroventricularly (1, 2, 2.5 or 4 μg/rat) produced the maximal decrease in gastric emptying and intestinal transit at the dose of 2.5 μg/rat. Higher doses produced a lower effect. Peripheral administration (25, 50 or 100 μg/kg) produced dose-dependent effects. Pre-treatment with neostigmine blocked the effect of amylin when it was centrally injected, while the effect of amylin given peripherally was partially reduced. Pre-treatment with domperidone decreased the inhibitory effect of peripherally injected amylin, but no effect was observed when the peptide was centrally injected.

Hypoprolactinemic Action of Calcitonin and the Tuberoinfundibular Dopaminergic System

Abstract: The effects of calcitonin on neurochemical parameters related to the tuberoinfundibular dopaminergic system have been investigated in an attempt to elucidate how calcitonin decreases serum prolactin levels. Intracerebroventricular human or salmon calcitonin injection decreases serum prolactin, medial basal hypothalamic dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) and hypophysial DA and increases hypophysial DOPAC. Results suggest that calcitonin may decrease prolactin secretion via the tuberoinfundibular dopaminergic system.

Anti-inflammatory activity of amylin and CGRP in different experimental models of inflammation

The anti-inflammatory activity of amylin was studied in different models of inflammation, and compared to that of CGRP. Both peptides were active against mouse ear oedema induced by croton oil and acetic acid-induced peritonitis in the rat. CGRP was more potent than amylin in both models. Pretreatment with CGRP 8-37 fragment blocked the anti-inflammatory activity of both peptides in croton oil ear oedema. No anti-inflammatory activity was evidenced against serotonin-induced rat paw oedema and plasma protein extravasation induced by dextran in rat skin. Our results suggest that amylin exerts anti-inflammatory activity only in inflammatory models characterized by a vascular component. This effect appears to be mediated by the involvement of CGRP receptors.

Antiinflammatory activity of adrenomedullin in the acetic acid peritonitis in rats.

The antiinflammatory effect of ADM was studied in different models of inflammation and compared to the one of CGRP. Peptides were active against acetic acid-induced peritonitis in the rats. ADM and CGRP exerted the antiinflammatory effect at different doses, 400 and 20 ng/kg respectively, but with different efficacy (ADM >CGRP). This effect was blocked by pretreatment with CGRP (8-37) fragment or with L-NAME. No antiinflammatory activity was evidenced against serotonin- or carrageenin-induced rat paw edema. Our data suggest that ADM exerts antiinflammatory activity in the model characterized by a vascular component. This effect involves CGRP receptors and appears to be mediated by nitric oxide system.

Protective effects of calcitonin gene-related peptide in different experimental models of gastric ulcers

Intravenous administration of calcitonin gene-related peptide (CGRP) prevented in a dose-dependent manner reserpine-induced gastric mucosal damage, but failed to affect the lesions produced by ethanol administration. In pylorus-ligated rats, CGRP significantly reduced gastric volume, total acid and peptic activity output as well as ulcer formation. These protective effects of CGRP were not present when rats were pretreated with cysteamine. Our data suggest that CGRP exerts its antisecretory and antiulcer activity, at least in part, by interfering with somatostatin transmission.

Effects of calcitonin, parathyroid hormone and its related fragments on acquisition of active avoidance behavior

The acquisition of active avoidance response was studied in rats injected intracerebroventricularly with calcitonin (CT), parathyroid hormone (PTH) or PTH-related fragments. PTH and PTH65-84 facilitated the acquisition of shuttle-box active avoidance behavior as indicated by the number of conditioned avoidance responses and the percentage of animals reaching the learning criterion. PTH1-34 and PTH44-68, on the contrary, inhibited the acquisition of active avoidance behavior, while CT totally suppressed this behavior in the rat. It is possible that the opposite effects of PTH and CT on learning ability of the rat depend on a different action on calcium metabolism.

Effects of CGRP in different models of mouse ear inflammation

The anti-inflammatory activity of calcitonin gene-related peptide (CGRP) has been studied in cutaneous inflammation induced by croton oil (CO), arachidonic acid (AA), tetradecanoylphorbol acetate (TPA) or cantharidin (CA). Our results show that mouse ear inflammation induced by CO, AA or TPA is decreased by topical administration of CGRP, whereas that induced by CA is not affected. The dose-response and temporal analysis of CGRP effect show that the maximal activity is present at the dose of 30 pmol/ear and when administered 30 min after the irritating agent. Moreover, pretreatment with capsaicin is able to mimic the anti-inflammatory effect of exogenous CGRP, while simultaneous administration of CGRP and capsaicin produces a reduced response. Our results suggest that CGRP released from sensory.

Adrenomedullin and ocular inflammation in the rabbit

Adrenomedullin administered peripherally in the rabbit (at doses of 1.25, 2.5 and 5 microg/kg ) caused a dose-dependent conjunctival hyperemia accompanied by an increase of inflammatory cell number and prostaglandin E(2) concentration in the aqueous humor, and of uveal vascular response and myeloperoxidase activity. The inflammatory effect of the peptide, injected at the dose of 5 microg/kg, was abolished by pretreatment with the inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methylester (50 mg/kg, i.v.). Moreover, the i.v. pretreatment with the calcitonin gene-related peptide 8-37 fragment (calcitonin gene-related peptide, CGRP-(8-37), 2.5 microg/kg), receptor antagonist of CGRP, did not inhibit the conjunctival hyperemia. In contrast, the i.v. pretreatment with the adrenomedullin receptor antagonist, adrenomedullin-(22-52) fragment (2.5 microg/kg), abolished adrenomedullin-induced ocular inflammation. These results suggest that adrenomedullin causes conjunctival hyperemia, and this effect involves the nitric oxide system acting through specific adrenomedullin receptors.

Behavioral effects of amylin injected intracerebroventricularly in the rat

Amylin is a peptide of pancreatic origin that has been reported to possess high-affinity binding sites in the brain and to affect central dopaminergic and serotonergic neurotransmission. Administered ICV the peptide induced a dose-dependent decrease of locomotor activity without affecting grooming and sniffing. At a dose of 5 micrograms/ rat, it antagonized the hypermotility and stereotypies induced by s.c. injection of amphetamine (2 mg/kg) or of the dopamine receptor agonist, apomorphine (250 mg/kg). Amylin did not change significantly the effect of haloperidol (0.5 mg/kg, s.c.) on locomotor activity, grooming, and sniffing. Moreover, the peptide did not modify the locomotor behavior of animals injected with the 5-HT2 antagonist, ritanserin (2 mg/kg, s.c.). These results suggest that amylin may exert motor effects, probably by interfering with central dopaminergic neurotransmission.

Effects of calcitonin gene-related peptide on extrapyramidal motor system

The effects of central administration of calcitonin gene-related peptide (CGRP, 1 or 100 ng/rat) on behavioral and biochemical parameters related to the extrapyramidal motor system were investigated in male rats. The peptide-induced catalepsy occurred only at the dose of 100 ng/rat and hypomotility at both doses used. Calcitonin gene-related peptide increased haloperidol-induced catalepsy and decreased apomorphine-induced hypermotility at the doses of 1 and 100 ng/rat. Although these behaviors are related to dopamine, no significant change of striatal DA or DOPAC concentration were observed after central administration of the peptide. Other neurotransmitters may be directly or indirectly involved in these behavioral effects of CGRP.