Species differences in histamine receptors in the vas deferens

Mm, Vohra

doi:10.1007/bf01967616

Cited by 15 publications

(12 citation statements)

References 14 publications

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“…Cimetidine abolished this effect of histamine, thus confirming our previous findings [1,2] that histamine inhibition is mediated by H2-receptors in the preparation. The cyclic nucleotides and phosphodiesterase inhibitors that we tested also produced inhibition.…”

Section: Discussionsupporting

confidence: 90%

“…Earlier reports from this laboratory showed that histamine inhibits the contractile response of the mouse vas deferens to electrical field stimulation and to exogenous noradrenaline [ 1,2]. This inhibition is antagonized by cimetidine but not by mepyramine, suggesting that the mouse vas deferens contains a cimetidine-sensitive, inhibitory H2-receptor.…”

Section: Introductionmentioning

confidence: 85%

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Effect of cyclic AMP, db-cyclic AMP and phosphodiesterase inhibitors on histamine inhibition of the contractile response of the mouse vas deferens

Vohra

1984

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Histamine inhibited the contractile response of the mouse vas deferens to various frequencies of stimulation, and the inhibition was inversely related to the frequency of stimulation. This effect of histamine was mimicked by cyclic AMP, db-cyclic AMP and various phosphodiesterase inhibitors (IBMX, aminophylline and theophylline). Histamine-produced inhibition, but not that produced by the other compounds, was blocked by cimetidine. The low concentrations (10-100 microM) of various phosphodiesterase inhibitors caused inhibition but failed to potentiate the inhibitory response to histamine. The basal cyclic AMP levels of the tissues were unaffected at these concentrations of aminophylline. At higher concentrations (1 and 5 mM), however, aminophylline significantly elevated the basal cyclic AMP levels of the tissues and markedly inhibited the contractile response to various frequencies of stimulation but still failed to enhance or potentiate the inhibitory response to histamine. In fact, the inhibitory response to histamine at these concentrations of aminophylline was reduced. Based on these and earlier [3] findings, it is concluded that, although histamine increases the accumulation of cyclic AMP in the mouse vas deferens and although its inhibitory effect on the preparation can be mimicked by both the cyclic nucleotides and phosphodiesterase inhibitors, the involvement of cyclic AMP in the mediation of its inhibitory response is still unresolved.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 85%

Effect of cyclic AMP, db-cyclic AMP and phosphodiesterase inhibitors on histamine inhibition of the contractile response of the mouse vas deferens

Vohra

1984

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“…The activation of H 2 receptors by histamine inhibits the muscle contraction response due to a decrease in the Ca 2+ influx necessary for contraction. However, this effect (muscle relaxing) is reduced or totally antagonized by cimetidine [8,42], leading to increased intracellular calcium influx. The excess of calcium ions seems to be one of the main routes involved in the induction of programmed cell death [43,44].…”

Section: Discussionmentioning

confidence: 99%

NF-kB overexpression and decreased immunoexpression of AR in the muscular layer is related to structural damages and apoptosis in cimetidine-treated rat vas deferens

Koshimizu

Beltrame

Pizzol

et al. 2013

Reprod Biol Endocrinol

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BackgroundCimetidine, histamine H2 receptors antagonist, has caused adverse effects on the male hormones and reproductive tract due to its antiandrogenic effect. In the testes, peritubular myoid cells and muscle vascular cells death has been associated to seminiferous tubules and testicular microvascularization damages, respectively. Either androgen or histamine H2 receptors have been detected in the mucosa and smooth muscular layer of vas deferens. Thus, the effect of cimetidine on this androgen and histamine-dependent muscular duct was morphologically evaluated.MethodsThe animals from cimetidine group (CMTG; n=5) received intraperitoneal injections of 100 mg/kg b.w. of cimetidine for 50 days; the control group (CG) received saline solution. The distal portions of vas deferens were fixed in formaldehyde and embedded in paraffin. Masson´s trichrome-stained sections were subjected to morphological and the following morphometrical analyzes: epithelial perimeter and area of the smooth muscular layer. TUNEL (Terminal deoxynucleotidyl-transferase mediated dUTP Nick End Labeling) method, NF-kB (nuclear factor kappa B) and AR (androgen receptors) immunohistochemical detection were also carried out. The birefringent collagen of the muscular layer was quantified in picrosirius red-stained sections under polarized light. The muscular layer was also evaluated under Transmission Electron Microscopy (TEM).ResultsIn CMTG, the mucosa of vas deferens was intensely folded; the epithelial cells showed numerous pyknotic nuclei and the epithelial perimeter and the area of the muscular layer decreased significantly. Numerous TUNEL-labeled nuclei were found either in the epithelial cells, mainly basal cells, or in the smooth muscle cells which also showed typical features of apoptosis under TEM. While an enhanced NF-kB immunoexpression was found in the cytoplasm of muscle cells, a weak AR immunolabeling was detected in these cells. In CMTG, no significant difference was observed in the birefringent collagen content of the muscular layer in comparison to CG.ConclusionsCimetidine induces significant damages in the epithelium; a possible antiandrogenic effect on the basal cells turnover should be considered. The cimetidine-induced muscle cells apoptosis confirms the susceptibility of these cells to this drug. The parallelism between enhanced cytoplasmic NF-kB immunolabeling in the damaged muscular tissue and muscle cell apoptosis suggests that this drug may avoid the translocation of NF-kB to the nucleus and interfere in the control of NF-kB-mediated smooth muscle cell apoptosis. The decreased immunoexpression of ARs verified in the damaged muscular tissue reinforces this possibility.

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“…Previous work has indicated that guinea pig vasa deferentia are endowed with pre‐synaptic inhibitory HA H 3 receptors (Luo et al. 1994) and post‐synaptic excitatory H 1 receptors (Vohra 1981; Tamesue et al. 1998; Smith and Burnstock 2004).…”

Section: Discussionmentioning

confidence: 99%

Sympathetic histamine exerts different pre‐ and post‐synaptic functions according to the frequencies of nerve stimulation in guinea pig vas deferens

He¹,

Hu²,

Ma³

et al. 2008

Journal of Neurochemistry

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Histamine (HA) was found to be present in the sympathetic nerve terminals of guinea pig hearts and vasa deferentia in our previous study; however, little is known about the functions of this neurogenic HA. In this study, we used guinea pig vasa deferentia to investigate the pre‐ and post‐synaptic functions of HA evoked by different frequencies of sympathetic nerve stimulation. We found that sympathetic nerve stimulation could evoke HA release, which was independent to mast cell degranulator compound 48/80 and mast cell stabilizer cromolyn, but was highly sensitive to Na+ channel blocker tetrodotoxin and chemical sympathectomy with 6‐hydroxydopamine. The neurogenically released HA evoked by 12.5 Hz of nerve stimulation activated only pre‐synaptic H3 receptors and mediated pre‐synaptic inhibitory effects, while under 25 or 50 Hz stimulation condition, HA simultaneously activated both pre‐synaptic H3 receptors and post‐synaptic H1 receptors. However, the direct contractile responses evoked by sympathetic HA via H1 receptors were observed at 50 Hz. HA release and HA‐mediated contractile responses upon sympathetic nerve stimulation were significantly inhibited by pre‐treatment of histidine decarboxylase inhibitor α‐fluoromethylhistidine. Furthermore, application of exogenous HA could mimic these pre‐ and post‐synaptic effects. Our findings indicate that HA in sympathetic neurons acts as a neurotransmitter and its functions vary from pre‐synaptic inhibition, to post‐synaptic facilitation, to direct post‐synaptic contractile responses according to sympathetic nerve stimulation frequencies.

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Species differences in histamine receptors in the vas deferens

Cited by 15 publications

References 14 publications

Effect of cyclic AMP, db-cyclic AMP and phosphodiesterase inhibitors on histamine inhibition of the contractile response of the mouse vas deferens

Effect of cyclic AMP, db-cyclic AMP and phosphodiesterase inhibitors on histamine inhibition of the contractile response of the mouse vas deferens

NF-kB overexpression and decreased immunoexpression of AR in the muscular layer is related to structural damages and apoptosis in cimetidine-treated rat vas deferens

Sympathetic histamine exerts different pre‐ and post‐synaptic functions according to the frequencies of nerve stimulation in guinea pig vas deferens

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