The Journal of veterinary medical science
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Proteinase-activated receptor (PAR) is expressed on various cells, and the PAR family consists of PAR1, PAR2, PAR3, and PAR4. Individual PARs are activated during inflammatory conditions in which they regulate inflammatory responses in various diseases. For example, PAR activation is known to induce prostaglandin E2 (PGE2) production, and then upregulated PGE2 suppresses PAR1 expression in a negative feedback loop. ⋯ Furthermore, forskolin, an adenylate cyclase activator, induced PAR2 internalization and inhibited PAR2-AP-induced phosphorylation of ERK. Because EP2 (not EP1) also increases intracellular cyclic AMP, we conclude that PGE2 inhibited PAR2-dependent signal transduction by inducing the internalization of PAR2 through an EP2-dependent increase in intracellular cyclic AMP. This novel regulatory pathway in which PAR2 function is regulated by PGE2 will broaden our understanding of PAR2-dependent inflammation and could provide novel strategies for drug development.
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Comparative Study
Distribution of contrast medium epidurally injected at thoracic and lumbar vertebral segments.
The epidural distribution of iohexol (0.2 ml/kg) administered at thoracic vertebrae (Thoracic group) and lumbar vertebrae (Lumbar group) was compared by computed tomographic (CT) epidurography in dogs. The total spread of iohexol was similar between the 2 groups upon reaching a similar cranial level. The maximal CT values were higher at the C7/T1 and T4/T5 levels in Thoracic group, but they were higher at the T13/L1 and L4/L5 levels in Lumbar group (P<0.05). This result suggests that the distribution pattern of the drug administered epidurally at thoracic vertebrae and lumbar vertebrae is different in dogs.
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Tramadol is an atypical opioid analgesic widely used in small animal practice. This study was designed to determine the effect of a single intravenous (IV) dose of tramadol on the minimum alveolar concentration (MAC) of sevoflurane in dogs. Six beagle dogs were anesthetized twice to determine the sevoflurane MAC with or without an administration of tramadol (4 mg/kg, IV) at 7 days interval. ⋯ The dogs that received tramadol treatment sometimes breathed spontaneously. Therefore, their respiratory rates significantly increased, and PETCO2 decreased during the MAC determination. In conclusion, the single IV dose of tramadol produced a significant reduction in the sevoflurane MAC in dogs.