Antidipsogenic effects of central adenosine-5'-triphosphate

Abstract

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% 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% 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% 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.

IV Miguel R. Covian Symposium: new challenges for physiologists

“…Nascimento and Branco (5) suggested an interesting synergism between peripheral and spinal heme oxygenase-carbon monoxide pathways that may play an antinociceptive role. Evidence was presented by de Faria et al (6) that activation of purinergic receptors in the brain may affect water intake in animals submitted to dehydration. Burnstock (7) reviewed the history of his discovery of purinergic transmission and the role of ATP as a cotransmitter in all nerves of the peripheral and central nervous systems.…”