Antidipsogenic effects of central adenosine-5'-triphosphate

Besides other physiological functions, adenosine-5'-triphosphate (ATP) is also a neurotransmitter that acts on purinergic receptors. In spite of the presence of purinergic receptors in forebrain areas involved with fluid-electrolyte balance, the effect of ATP on water intake has not been investigated. Therefore, we studied the effects of intracerebroventricular (icv) injections of ATP (100, 200 and 300 nmol/µL) alone or combined with DPCPX or PPADS (P1 and P2 purinergic antagonists, respectively, 25 nmol/µL) on water intake induced by water deprivation. In addition, the effect of icv ATP was also tested on water intake induced by intragastric load of 12 percent NaCl (2 mL/rat), acute treatment with the diuretic/natriuretic furosemide (20 mg/kg), icv angiotensin II (50 ng/µL) or icv carbachol (a cholinergic agonist, 4 nmol/µL), on sodium depletion-induced 1.8 percent NaCl intake, and on food intake induced by food deprivation. Male Holtzman rats (280-320 g, N = 7-11) had cannulas implanted into the lateral ventricle. Icv ATP (300 nmol/µL) reduced water intake induced by water deprivation (13.1 ± 1.9 vs saline: 19.0 ± 1.4 mL/2 h; P < 0.05), an effect blocked by pre-treatment with PPADS, but not DPCPX. Icv ATP also reduced water intake induced by NaCl intragastric load (5.6 ± 0.9 vs saline: 10.3 ± 1.4 mL/2 h; P < 0.05), acute furosemide treatment (0.5 ± 0.2 vs saline: 2.3 ± 0.6 mL/15 min; P < 0.05), and icv angiotensin II (2.2 ± 0.8 vs saline: 10.4 ± 2.0 mL/2 h; P < 0.05), without changing icv carbachol-induced water intake, sodium depletion-induced 1.8 percent NaCl intake and food deprivation-induced food intake. These data suggest that central ATP, acting on purinergic P2 receptors, reduces water intake induced by intracellular and extracellular dehydration.

Involvement of adenosinergic receptors in anxiety related behaviours.

In the present study, the effect of adenosine (A1 and A2 receptor agonist), caffeine (A2A receptor antagonist), theophylline (A2A receptor antagonist) and their combination was studied in anxiety related behaviours using elevated zero maze and elevated plus maze paradigms and compared their various behavioural profiles. Adenosine (10, 25, 50,100 mg/kg) significantly showed anxiolytic effect at all the doses, whereas caffeine (8, 15, 30, 60 mg/kg) and theophylline (30, 60 mg/kg) showed psychostimulatory action at lower doses and anxiogenic effect at higher doses. Pretreatment with caffeine (8, 15, 30 mg/kg) and theophylline (30 mg/kg) reversed the anxiolytic effect of adenosine. The study suggested the involvement of adenosinergic receptor system in anxiety related behaviours.

La activación de los receptores A1 de adenosina atenua el atontamiento de miocardio en el conejo / The activation of A1 adenosine receptors attenuates myocardial stunning in the rabbit

Los corazones expuestos a un período prolongado de isquemia (ü 30 minutos) presentan un menor tamaño de infarto cuando son reperfundidos en presencia de adenosina. Sin embargo, cuando el período de isquemia es menor, estas áreas de infarto son poco significativas, quedando en forma transitoria un cuadro de disfunción ventricular postisquémica. El objetivo del presente trabajo fue determinar el efecto de la adenosina, (administrada solamente en la reperfusión) sobre las alteraciones sistólicas y diastólicas presentes en la disfunción ventricular postisquémica así como también determinar sí en dicho efecto están involucrados los receptores A1. Corazones aislados e isovolúmicos de conejo, fueron sometidos a isquemia global de 15 minutos y reperfusión de 30 minutos. Durante la reperfusión se evaluó la función ventricular. En el grupo control, la presión desarrollada (PDVI) se recuperó hasta un 56ñ2% a los 30 minutos de la reperfusión, mientras que con la administración de adenosina alcanza un 75ñ3% (P<0.05 vs. control) Sin embargo, cuando se administró la adenosina junto con el bloqueante selectivo del receptor A1 (DPCPX) la PDVI alcanzó un 50ñ2% (P<0.05 vs. control). La presión diastólica final (PDFVI) (rigidez diastólica) en el grupo control, aumentó un 293ñ4%, a los 30 minutos de la reperfusión, mientras que con la administración de adenosina, la PDFVI alcanzó un 15ñ8% (P<0.05 vs. control). La reperfusión en presencia de adenosina más DPCPX no logró atenuar el aumento de la rigidez diastólica, alcanzando un 493ñ9 % (P<0.05 vs. control). La adenosina atenuó las alteraciones sistólicas y la rigidez diastólica de la disfunción postisquémica. Este efecto protector fue abolido por el bloqueante de los receptores A1, sugiriendo un rol de estos receptores en la protección inducida por adenosina

Influência da cafeína no comportamento da pressäo arterial e da agregaçäo plaquetária / Influence of caffeine on blood pressure and platelet aggregation

OBJECTIVE: Studies have demonstrated that methylxanthines, such as caffeine, are A1 and A2 adenosine receptor antagonists found in the brain, heart, lungs, peripheral vessels, and platelets. Considering the high consumption of products with caffeine in their composition, in Brazil and throughout the rest of the world, the authors proposed to observe the effects of this substance on blood pressure and platelet aggregation. METHODS: Thirteen young adults, ranging from 21 to 27 years of age, participated in this study. Each individual took 750mg/day of caffeine (250mg tid), over a period of seven days. The effects on blood pressure were analyzed through the pressor test with handgrip, and platelet aggregation was analyzed using adenosine diphosphate, collagen, and adrenaline. RESULTS: Diastolic pressure showed a significant increase 24 hours after the first intake (p<0.05). This effect, however, disappeared in the subsequent days. The platelet aggregation tests did not reveal statistically significant alterations, at any time during the study. CONCLUSION: The data suggest that caffeine increases diastolic blood pressure at the beginning of caffeine intake. This hypertensive effect disappears with chronic use. The absence of alterations in platelet aggregation indicates the need for larger randomized studies.

Influence of adenosine agonists and antiepileptic drugs on theophylline-induced seizures in rats.

Seizures is a major toxicity of theophylline. The mechanism of theophylline-induced seizures is not known, but antagonism at adenosine receptors may be a possibility. The effect of pretreatment with different doses of adenosine (100, 500 and 1000 mg/kg, i.p.), and the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA), 1, 5 and 10 mg/kg, i.p., was studied against seizures induced by theophylline in rats. Both these drugs, at all dose levels tested, failed to protect theophylline seizures. Thus adenosinergic system is unlikely to be involved in mediating the convulsant action of theophylline. On the other hand, the conventional antiepileptic drugs, i.e. diazepam (4 mg/kg), sodium valproate (300 mg/kg) and phenobarbitone (50 mg/kg), but not carbamazepine, afforded some protection. The modification of course of seizures, by the antiepileptic drugs suggests the involvement of some other alternate mechanism in theophylline-induced seizures.