Changes of PACAP levels in the brain show gender differences following short-term water and food deprivation.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a pleiotropic neuropeptide exerting diverse actions in the central and peripheral nervous systems. A few studies indicate that PACAP is involved in the regulation of feeding and water homeostasis. The aim of the present study was to investigate changes in PACAP38 concentrations in different brain areas following food or water deprivation in male and female rats. Rats were sacrificed 12, 36 and 84h after water or food removal. PACAP levels were determined by radioimmunoassay. Our results show that levels of PACAP decreased in the hypothalamus in both sexes after water deprivation, with a more marked, significant decrease in females at 12h. A decrease was observed also in the telencephalon, with a similar pattern in both genders: levels were lowest after 12h, and showed a gradual increase at the other two time-points. PACAP levels increased in the brainstem of male rats, while females had a decrease 12h after water deprivation. The pattern of changes in PACAP levels was very different after food deprivation. In male rats, PACAP levels showed a significant increase in the hypothalamus, telencephalon and brainstem 12h after the beginning of starvation. In females, a less marked increase was observed only in the hypothalamus while no changes were found in the other brain areas. Our results show a sensitive reaction in changes of endogenous PACAP levels to water and food deprivation in most brain areas, but they are differentially regulated in male and female rats.

Systemic anti-inflammatory effect of somatostatin released from capsaicin-sensitive vagal and sciatic sensory fibres of the rat and guinea-pig.

The systemic anti-inflammatory effect induced by antidromic sensory nerve stimulation was investigated in rats and guinea-pigs. In atropine-pretreated rats, bilateral antidromic stimulation of vagal afferent fibres (8 Hz, 20 min, at C-fibre strength) inhibited plasma extravasation induced by 1% mustard oil on the acutely denervated hindlegs by 36.45+/-3.95%. Both the prevention of this inhibitory effect by cysteamine pretreatment and the stimulation-evoked rise of plasma somatostatin-like immunoreactivity in the two species suggest a mediator role of neural somatostatin. Since this response was blocked by systemic capsaicin pretreatment and slightly reduced after subdiaphragmal vagotomy, participation of thoracic capsaicin-sensitive afferents is indicated. In guinea-pigs pretreated with guanethidine and pipecuronium, antidromic sciatic nerve stimulation induced 45.46+/-5.08% inhibition on the contralateral leg and increased plasma somatostatin-like immunoreactivity. It is concluded that somatostatin released from the activated vagal capsaicin-sensitive sensory nerve terminals of the rat and somatic nerves of the guinea-pigs exerts a systemic humoral function.

7-oxo PGI2 dramatically increases the safety margin of digitalis.

In our earlier experiments pretreatment with 7-oxo PGI2 was found to be effective against ouabain induced rhythm disturbances in guinea pigs. Maximal protection appeared 48 hours after a single dose of 50 micrograms/kg administered i.m. In the present study we wanted to clarify how cardiac glycoside induced positive inotropic responses as well as appearance of rhythm disturbances in higher doses were influenced by 7-oxo PGI2 pretreatment in dogs. The experiments were performed on anesthetized, artificially ventilated mongrel dogs weighing 9-11 kg. The ECG, left ventricular pressure, as well as +dP/dtmax and -dP/dtmax were continuously recorded. Ouabain was applied by intermittent infusion, i.e. an initial i.v. dose of 30 micrograms/kg was infused during 5 min followed by a 25 min interval, then 15 micrograms/kg was infused every 10 min for 2.5 min until cardiac arrest. Ouabain induced increasingly severe patterns of rhythm disturbances, ventricular extrasystoles (ES), ventricular tachycardia (VT), ventricular fibrillation (VF) and cardiac arrest (CA). In the case of 7-oxo PGI2 (50 micrograms/kg) pretreatment the dose of ouabain necessary to provoke ES was 62 +/- 5.0 micrograms/kg versus (v.s.) 53.3 +/- 3.4 micrograms/kg in the control group, VT: 97 +/- 5.0 micrograms/kg v.s. 80 +/- 6.2 micrograms/kg and CA: 100 +/- 4.2 micrograms/kg v.s. 87 +/- 7.7 micrograms/kg. In the pretreated group 25% of the maximal positive inotropic effect was produced by 14.2 +/- 3.6 micrograms/kg ouabain v.s. 31.7 +/- 3.6 micrograms/kg. According to the above results 7-oxo PGI2 increases the safety margin of ouabain.