Involvement of purinergic signalling in central mechanisms of body temperature regulation in rats

Abstract

1. P2 purinoreceptors are present in hypothalamic and brainstem nuclei that are involved in the regulation of body temperature (Tb). The role of ATP acting on these P2 receptors in thermoregulation was investigated by studying the effects of the stable ATP analogue α, β-methyleneATP (α, β-meATP) and P2 receptor antagonists suramin and pyridoxal-5′-phosphate-6azophenyl-2′, 4′-disulphonic acid (PPADS) on Tb when injected intracerebroventricularly (i.c.v.) via a pre-implanted cannula in conscious rats at various ambient temperatures and during lipopolysaccharide (LPS)-induced fever. 2. Depending on ambient temperature, α, β-meATP (0.2 μmol, i.c.v. induced a fall in Tb (-3.3°C, P<0.05), no changes in Tb when compared to pre-injection levels, or an increase in Tb (- 1.0°C, P<0.05) in rats maintained at 10°C, 25°C and 30°C ambient temperature, respectively. 3. Suramin (7 nmol, i.c.v.) induced a lasting (up to 6 h) increase in Tb (on average 1.2°C, P<0.05) in rats kept at 25°C or 30°C, but failed to induce any rise in Tb in rats at 10°C ambient temperature. An increase in Tb was also observed in rats (25°C ambient temperature) treated with PPADS (0.2 μmol, i.c.v.). 4. α, β-meATP (0.2 μmol) injected i.c.v. or directly into the anterior hypothalamus caused a profound fall in Tb (by 0.9°C and 1.0°C, respectively; P<0.05) during LPS (E.coli; 50 μg kg-1)-induced fever in rats at 25°C ambient temperature. Fever was initiated more rapidly in rats treated with suramin (7 nmol) or PPADS (70 nmol), however its late phase was unaffected. Suramin (7 nmol) and PPADS (70 nmol) injected at the time when fever was already developed (2.5 h after LPS injections) did not alter febrile Tb. 5. These data indicate that purinergic signalling may play a significant role in central mechanisms of Tb regulation at various ambient temperatures and during fever.