ABSTRACT
Metoclopramide (MCP) has been demonstrated to restore the depressed cellular immune function after hemorrhage by increasing the release of the immunomodulatory pituitary hormone prolactin. We investigated the effect of MCP on serum prolactin concentrations, on cellular immune functions (immune cell distribution, splenocyte proliferation, apoptosis and cytokine release) and on the survival 48 h after induction of a polymicrobial sepsis in mice. Administration of MCP increased circulating serum prolactin concentrations and splenocyte apoptosis rate and improved cellular cytokine release, but did not affect mortality of septic mice. We therefore conclude that administration of MCP modulated splenocyte apoptosis and cytokine release in a murine model of sepsis without an impact on the survival. Furthermore, this effect may be mediated by an increased endogenous prolactin release.
Subject(s)
Dopamine Antagonists/pharmacology , Immunity, Cellular/drug effects , Metoclopramide/pharmacology , Sepsis/immunology , Animals , Apoptosis/immunology , Cytokines/biosynthesis , Cytokines/immunology , Dopamine Antagonists/immunology , Immunity, Cellular/immunology , Male , Metoclopramide/immunology , Mice , Models, Animal , Prolactin/blood , Sepsis/complications , Sepsis/drug therapy , Spleen/cytology , Spleen/immunology , Survival Analysis , Systemic Inflammatory Response Syndrome/immunologyABSTRACT
To develop a sensitive and simple assay method for 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), an endogenous parkinsonism-preventing substance, we designed two kinds of 1MeTIQ-bovine serum albumin (BSA) conjugates to recognize the methyl group at the 1 position of 1MeTIQ since this is the critical structural difference between 1MeTIQ and parkinsonism-inducing substances. These hapten antigens were synthesized from 1MeTIQ analogues and BSA. A specific antiserum against 1MeTIQ was obtained from a rabbit immunized with one of the hapten antigens. To utilize this antiserum for radioimmunoassay, detailed studies were carried out to establish optimum conditions. The antiserum recognized 1MeTIQ and showed little cross-reactivity with endogenous 1MeTIQ analogues and proteins. It was confirmed to be suitable for radioimmunoassay, and a standard curve was prepared in the range of 0.5 to 100 pmol of 1MeTIQ. This method was sensitive enough to measure endogenous 1MeTIQ in rat brain. This method should be applicable for evaluation of the progression or prognosis of Parkinson's disease (PD).
