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Chronic alveolar hypoxia in rat is associated with a significant increase, about 73%, in lung adrenomedullin (AM) and calcitonin gene-related peptide binding sites. It also enhances the hypotensive response of the pulmonary circulation to the peptides. Calcitonin gene-related peptide is more potent than AM as tachyphylaxis with the latter is less marked than with the former. AM may be used for the acute pharmacological manipulation of pulmonary circulation.

Background: Epigenetic mechanisms such as histone modifications may be involved in the structural and behavioral changes associated with addiction. We studied whether morphine-induced changes in mRNA levels of the catecholamine biosynthesis enzyme, tyrosine hydroxylase (TH), are associated with histone modifications around the promoter of this gene in the locus coeruleus (LC) and ventral tegmental area (VTA) of rats.Methods: Dependence was induced in rats by intraperitoneal injections of morphine for 11 days. The animals were killed 2 h (chronic morphine), 24 h and 7 days (spontaneous withdrawal) after the last injection of morphine.Results: Analysis of our real-time quantitative reverse transcription PCR results by 1-way ANOVA showed significant upregulation (5.13 ± 0.39 folds) of LC levels of the TH transcript 24 h after the last injection of morphine to rats, when compared with 2 h and 7 days time points. Chronic morphine and morphine abstinence failed to cause any significant changes in the levels of TH mRNA in the VTA after cessation of morphine. Consistently, chromatin immunoprecipitation real-time quantitative PCR assays revealed that 24 h after the last injection of morphine, levels of H3 acetylation were significantly increased (4.12 ± 0.38 folds) at the promoter of the TH gene in the LC but not in the VTA. Our data also showed that histone H3 trimethylation failed to change around the TH gene promoter either in the VTA or in the LC after morphine abstinence.Conclusions: Results of the present study, for the first time, demonstrate the involvement of histone H3 acetylation in the regulation of TH gene expression in the LC of rats during forced abstinence from morphine. [ABSTRACT FROM AUTHOR]

Objective(s): Systemic and intracerebroventricular (ICV) injection of insulin possess analgesic effects. The raphe magnus nucleus (RMN) is part of the endogenous analgesia system. The objective of the present study was to evaluate the effects of ICV injection of insulin on the levels of monoamines and their related metabolites in the RMN during the formalin test in non-diabetic and short-term diabetic rats. Materials and Methods: Sixty four adult male rats were used. Diabetes was induced by Streptozotocin (STZ) (60 mg/kg, IP); insulin (5 mU/animal, 5 μl) was injected into the left ventricle. Microdialysis was performed in each rat. Samples were collected at 15 min intervals. After taking the base sample of microdialysis, 50 μl of 2.5% formalin was injected into the plantar surface of the hind paw, and the level of nociception was recorded every 15 sec for 1 hr. Monoamines and their metabolites concentrations were measured using the HPLC-ECD method. Results: Findings showed that ICV injection of insulin in non-diabetic rats increased the concentration of monoamines and their related metabolites in the RMN. In diabetic rats, injection of insulin decreased the concentrations of monoamines and their related metabolites in the RMN (P<0.05). Our results determined that, at least in part, insulin is associated with antinociceptive effect in non-diabetic rats. Conclusion: Based on the results, it seems that ICV injection of insulin in non-diabetic rats increased the activity of the central pain control pathways leading to antinociceptive response, but this condition was not seen in diabetic rats. [ABSTRACT FROM AUTHOR]

Objective(s): Calcitonin gene related peptide (CGRP) receptors are widely distributed in the central nervous system. The aim of this study was to investigate the effects of intracerebroventricular (ICV) injection of CGRP on pain behavioral responses and on levels of monoamines in the periaqueductal gray area (PAG) during the formalin test in rats. Materials and Methods: Twenty-four male rats were studied in four groups (n=6). CGRP was injected into the left cerebral ventricle (1.5 nmol, 5 |il). After 20 min, formalin (2.5%) was subcutaneously injected into the right hind paw. Behavior nociceptive score was recorded up to 60 min. During the formalin test, the PAG was subjected to microdialysis and levels of norepinephrine, 3-methoxy-4-hydroxyphenyl-glycol (HMPG), dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin and 5-hydroxyindole-acetic acid (HIAA) were measured by HPLC. Results: ICV injection of CGRP lead to a significant pain reduction in acute, middle and chronic phases of the formalin test. Dialysate concentrations of norepinephrine, HMPG, dopamine, DOPAC, serotonin and HIAA in the PGA area showed an increase in acute phase, middle phase and beginning of the chronic phase of the formalin test. Conclusion: CGRP significantly reduced pain by increased concentrations of monoamines and their metabolites in dialysates from PAG when injected ICV to rats. [ABSTRACT FROM AUTHOR]