Central cardiovascular and thermal effects of prostaglandin D2 in rats

Abstract

Prostaglandin Dz (PGD z ) is the most common prostaglandin type of tile rat brain. Recently a neurornodulator role for PGD z has been suggested. In the present work the central cardiovascular and thermal effects of PGDz were studied in urethane-anaesthetised rats. Mlen adrndnistered at the doses of 0.001-10 ~g/rat into the lateral cerebral ventricle(i.c.v.), PGD2 slightly increased the blood pressure, heart rate and body ternperaure.The highest dose caused also an initial hypotensive effect. Upon lntravenous injections PGD2 (0.1-10 ~g/rat) initially decreased and then weakly increased the blood pressure but had only negligible effects on heart rate and body temperature. Central pretreatment with sodium meclofenamate or indomethacin (1 mg/rat i.c.v.) antagonised effectively all the recorded central effects of PGD2.The central cardiovascular and thermal effects of PGD 2 were much weaker than those obtained earlier with other prostaglandins, such as PGF2a. and PGE2.. Therefore, in spite of its ablUldance in the brain PGD 2 may not be very important for the central cardiovascular and thermal regulation in the rat.

Fever response to intravenous prostaglandin E2 is mediated by the brain but does not require afferent vagal signaling

“…The solutions of PGE 2 used in the present experiments in anesthetized vs. conscious rats were prepared differently: a hydroalcoholic solution of PGE 2 vs. a PGE 2 -BSA complex in saline, respectively. In agreement with the literature (11,15,58,65,79,80,82), both preparations caused comparable fevers at similar doses, thus confirming that physiologically active (monomeric) PGE 2 was successfully delivered to the receptors triggering the fever response. Furthermore, vagotomy had no effect on the febrile response to either preparation of PGE 2 .…”

“…Neutralization of circulating PGE 2 with anti-PGE 2 antibodies (which do not cross the BBB) also delays and attenuates (82) or even completely blocks (32) the early phase of LPS fever. Not surprisingly, intravenous or intracarotid PGE 2 or PGE 1 readily causes fever when administered in a monomeric form, that is, either with a sufficient amount of an organic solvent (such as ethanol) (11,15,58,79,80) or as a complex with serum albumin, a principal endogenous carrier of circulating PGE 2 (65,82). For comparison, several studies that used a low concentration of ethanol (or no ethanol) and/or a high concentration of PGE 2 or PGE 1 in the suspension injected intravenously or in the carotid artery failed to induce fever, presumably because the drug was administered in an aggregated form (see Ref.…”

Prostaglandin D2 DP1 receptor is beneficial in ischemic stroke and in acute exicitotoxicity in young and old mice

“…Although we did not investigate the role of DP1 in temperature regulation extensively, our data suggest that DP1 activation does not affect core body temperature in our experimental paradigm. It is noteworthy that a rat study predicted that despite its abundance in brain (Siren 1982), PGD 2 might not have an important role to play in central cardiovascular and thermal regulation. Moreover, Brus et al (1980) reported no changes in behavior, body temperature, or blood pressure of Wistar rats after ICV injection of PGD 2 .…”

Loss of microglial ramification in microglia‐astrocyte cocultures: Involvement of adenylate cyclase, calcium, phosphatase, and Gi‐protein systems

“…Severe brain injury is also known to cause enhanced synthesis and/or release of many different trauma-and inflammation-associated molecules, including cytokines, prostaglandins, proteases such as thrombin, as well as intracellular nucleotides. ATP and UTP are released from leaky, injured cells or due to strong electrical stimulation (Schipke et al, 2002), thrombin from coagulation sites and local synthesis in damaged tissue (Citron et al, 2000), and prostaglandin D 2 , the most common type of a brain prostaglandin (Siren, 1982), primarily from activated microglial cells (Matsuo et al, 1995;Minghetti and Levi, 1995). Interestingly, none of these molecules appears to exert a strong, ramificationinhibiting effect in the coculture system, although they do affect other parameters of microglial activation (Walz et al, 1993;Norenberg et al, 1997;Moller et al, 2000).…”