Basic & clinical pharmacology & toxicology
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Basic Clin. Pharmacol. Toxicol. · Aug 2006
Review Comparative StudyThe effect of vasopressin and related compounds at V1a and V2 receptors in animal models relevant to human disease.
Vasopressin, a neurohypophyseal peptide hormone, is the endogenous agonist at V1a, V1b and V2 receptors. The most important physiological function of vasopressin is the maintenance of water homeostasis through interaction with V2 receptors in the kidney. Vasopressin and related compounds are used in various clinical settings such as acute variceal bleeding associated with portal hypertension, septic shock, diabetes insipidus and coagulation disorders. ⋯ Vasopressin and related compounds have demonstrated activity in animal models of portal hypertension, sepsis and septic shock, diabetes insipidus and coagulation disorders. The use of the compounds in animal models is reviewed. Generally, the effect of vasopressin and related compounds in animal models reflect the activity in the clinical setting, but in some cases important species differences exist.
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Basic Clin. Pharmacol. Toxicol. · Aug 2006
Different patterns of spinal cyclooxygenase-1 and cyclooxygenase-2 mRNA expression in inflammatory and postoperative pain.
Levels of cyclooxygenase-2 (COX-2) mRNA, but not those of COX-1, were reported to be raised significantly after peripheral inflammation in the rat spinal cord. The aim of the present study was to ascertain whether this pattern of COX-2 and COX-1 expression applies also to other pain conditions induced by surgical procedure. Experiments were performed on two types of pain models. ⋯ Under the acute inflammation 2 and 6 hr after carrageenan injection levels of COX-2 mRNA were markedly raised (7.8 and 15.5 times; P<0.001, respectively) while spinal levels of COX-1 mRNA were not significantly altered (n.s.). In contrast, spinal levels of COX-2 mRNA were raised less markedly in a model of postoperative pain (4.9 times at 2 hr; P<0.001 and 2.9 times (n.s.) at 6 hr after surgery) whilst levels of COX-1 mRNA in the lumbar spine were increased significantly (2.3 times; P<0.001) 6 hr after surgery. The present findings indicate that expression of COX-2 mRNA in the spine is less dominant in postoperative pain than in inflammatory pain and that spinal COX-1 mRNA is upregulated in postoperative pain.