| 1. |
- Cao, Lei, et al.
(författare)
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Secondhand cigarette smoke induces increased expression of contractile endothelin receptors in rat coronary arteries via a MEK1/2 sensitive mechanism
- 2021
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 55:1, s. 50-55
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Cigarette smoke, a strong risk factor for cardiovascular diseases, upregulates contractile endothelin (ET) receptors in coronary arteries. The present study examined the effects of second hand cigarette smoke exposure on the contractile endothelin receptors and the role of the MEK1/2 pathway in rat coronary arteries. Design: Rats were exposed to secondhand smoke (SHS) for 8 weeks followed by intraperitoneal injection of a MEK1/2 inhibitor, U0126 daily for another 4 weeks. Contractile responses of isolated coronary arteries were recorded by a sensitive wire myograph. The receptor protein expression levels were examined by Western blotting. Results: The results showed that SHS in vivo caused increased expression of ET receptors ETA and ETB, and that the MEK1/2 blocker U0126 significantly reversed SHS exposure-increased ETA-mediated contractile responses and protein levels. Similar alterations were observed in ETB receptors. U0126 showed dose-dependent effects on SHS-induced response on contractile property and protein levels of the ETB receptor. However, only the higher dose U0126 (15 mg/kg) had inhibitory effects on the ETA receptor. Conclusions: Taken together, our data show that SHS increases contractile ET receptors and MEK1/2 pathway inhibitor offsets SHS exposure-induced ETA and ETB receptor upregulation in rat coronary arteries.
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| 2. |
- Christiansen, Isabella Mai, et al.
(författare)
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Dual action of the cannabinoid receptor 1 ligand arachidonyl-2′-chloroethylamide on calcitonin gene-related peptide release
- 2022
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Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 23
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Tidskriftsartikel (refereegranskat)abstract
- Background: Based on the current understanding of the role of neuropeptide signalling in migraine, we explored the therapeutic potential of a specific cannabinoid agonist. The aim of the present study was to examine the effect of the synthetic endocannabinoid (eCB) analogue, arachidonyl-2′-chloroethylamide (ACEA), on calcitonin gene-related peptide (CGRP) release in the dura and trigeminal ganglion (TG), as cannabinoids are known to activate Gi/o-coupled cannabinoid receptors type 1 (CB1), resulting in neuronal inhibition. Methods: The experiments were performed using the hemi-skull model and dissected TGs from male Sprague-Dawley rats. CGRP release was induced by either 60 mM K+ (for depolarization-induced stimulation) or 100 nM capsaicin (for transient receptor potential vanilloid 1 (TRPV1) -induced stimulation) and measured using an enzyme-linked immunosorbent assay. The analysis of CGRP release data was combined with immunohistochemistry in order to study the cellular localization of CB1, cannabinoid receptor type 2 (CB2), CGRP and receptor activity modifying protein 1 (RAMP1), a subunit of the functional CGRP receptor, in the TG. Results: CB1 was predominantly expressed in neuronal somas in which colocalization with CGRP was observed. Furthermore, CB1 exhibited colocalization with RAMP1 in neuronal Aδ-fibres but was not clearly expressed in the CGRP-immunoreactive C-fibres. CB2 was mainly expressed in satellite glial cells and did not show substantial colocalization with either CGRP or RAMP1. Without stimulation, 140 nM ACEA per se caused a significant increase in CGRP release in the dura but not TG, compared to vehicle. Furthermore, 140 nM ACEA did not significantly modify neither K+- nor capsaicin-induced CGRP release. However, when the TRPV1 blocker AMG9810 (1 mM) was coapplied with ACEA, K+-induced CGRP release was significantly attenuated in the TG and dura. Conclusions: Results from the present study indicate that ACEA per se does not exhibit antimigraine potential due to its dual agonistic properties, resulting in activation of both CB1 and TRPV1, and thereby inhibition and stimulation of CGRP release, respectively.
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| 3. |
- Edvinsson, Jacob Carl Alexander, et al.
(författare)
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Differences in pituitary adenylate cyclase-activating peptide and calcitonin gene-related peptide release in the trigeminovascular system
- 2020
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 40:12, s. 1296-1309
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several neurotransmitters are expressed in the neurons of the trigeminal ganglion. One such signalling molecule is the pituitary adenylate cyclase-activating peptide (PACAP). PACAP signalling has been suggested to have a possible role in the pathophysiology of primary headaches. Objective: The present study was designed to investigate the relationship between PACAP and calcitonin gene-related peptide, currently the two most relevant migraine peptides. Methods: In the current study, we used ELISA to investigate PACAP and calcitonin gene-related peptide release in response to 60 mM K+ or capsaicin using a rat hemi-skull model. We combined this analysis with qPCR and immunohistochemistry to study the expression of PACAP and calcitonin gene-related peptide receptors and ligands. Results: Calcitonin gene-related peptide (CGRP) is released from the trigeminal ganglion and dura mater. In contrast, PACAP is only released from the trigeminal ganglion. We observed a weak correlation between the stimulated release of the two neuropeptides. PACAP-38 immunoreactivity was expressed alone and in a subpopulation of neurons in the trigeminal ganglion that also store calcitonin gene-related peptide. The receptor subtype PAC1 was mainly expressed in the satellite glial cells (SGCs), which envelop the neurons in the trigeminal ganglion, in some neuronal processes, inside the Aδ-fibres and in the outermost layer of the myelin sheath that envelopes the Aδ-fibres. Conclusion: Unlike CGRP, PACAP is only released within the trigeminal ganglion. This raises the question of whether a migraine therapy aimed at preventing peripheral PACAP signalling would be as successful as the CGRP signalling targeted treatments.
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| 4. |
- Edvinsson, Jacob C.A., et al.
(författare)
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Neurokinins and their receptors in the rat trigeminal system : Differential localization and release with implications for migraine pain
- 2021
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Ingår i: Molecular Pain. - : SAGE Publications. - 1744-8069. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Substance P (SP) and calcitonin gene-related peptide (CGRP) have both been considered potential drug candidates in migraine therapy. In recent years, CGRP receptor inhibition has been established as an effective treatment, in particular as a prophylactic for chronic migraine. Curiously, inhibition of neurokinin receptor 1 (NK1R) failed to alleviate acute migraine attacks in clinical trials, and the neurokinins were consequently abandoned as potential antimigraine candidates. The reason behind this has remained enigmatic. Utilizing immunohistochemistry and semi-quantitative cell counts the expression of neurokinins and their associated receptors was examined in the rat trigeminal ganglion. Immunohistochemistry results revealed SP co-localization in CGRP positive neurons and C-fibres, where it mainly concentrated at boutons. Neurokinin A (NKA) was observed in a population of C-fibres and small neurons where it could co-localize with SP. In contrast, neurokinin B (NKB) did not co-localize with SP and was observed in large/medium sized neurons and Aδ-fibres. All neurokinin receptors (NK1-3R) were found to be expressed in a majority of trigeminal ganglion neurons and A-fibres. The functional release of SP and CGRP in the trigeminovascular system was stimulated with either 60 mM K+ or 100 nM capsaicin and measured with an enzyme-linked immunosorbent assay (ELISA). ELISA results established that SP can be released locally from trigeminovascular system. The released SP was comparatively minor compared to the CGRP release from stimulated dura mater, trigeminal ganglion neurons and fibres. We hypothesize that SP and CGRP signalling pathways may work in tandem to exacerbate painful stimuli in the TGV system.
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| 5. |
- Edvinsson, Jacob C.A., et al.
(författare)
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Neuropeptides and the Nodes of Ranvier in Cranial Headaches
- 2022
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 12
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Forskningsöversikt (refereegranskat)abstract
- The trigeminovascular system (TGV) comprise of the trigeminal ganglion with neurons and satellite glial cells, with sensory unmyelinated C-fibers and myelinated Aδ-fibers picking up information from different parts of the head and sending signals to the brainstem and the central nervous system. In this review we discuss aspects of signaling at the distal parts of the sensory fibers, the extrasynaptic signaling between C-fibers and Aδ-fibers, and the contact between the trigeminal fibers at the nerve root entry zone where they transit into the CNS. We also address the possible role of the neuropeptides calcitonin gene-related peptide (CGRP), the neurokinin family and pituitary adenylyl cyclase-activating polypeptide 38 (PACAP-38), all found in the TGV system together with their respective receptors. Elucidation of the expression and localization of neuropeptides and their receptors in the TGV system may provide novel ways to understand their roles in migraine pathophysiology and suggest novel ways for treatment of migraine patients.
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| 6. |
- Maddahi, Aida, et al.
(författare)
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Progesterone distribution in the trigeminal system and its role to modulate sensory neurotransmission : influence of sex
- 2023
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Ingår i: Journal of Headache and Pain. - 1129-2369. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Women are disproportionately affected by migraine, representing up to 75% of all migraine cases. This discrepancy has been proposed to be influenced by differences in hormone levels between the sexes. One such hormone is progesterone. Calcitonin gene-related peptide (CGRP) system is an important factor in migraine pathophysiology and could be influenced by circulating hormones. The purpose of this study was to investigate the distribution of progesterone and its receptor (PR) in the trigeminovascular system, and to examine the role of progesterone to modulate sensory neurotransmission. Methods: Trigeminal ganglion (TG), hypothalamus, dura mater, and the basilar artery from male and female rats were carefully dissected. Expression of progesterone and PR proteins, and mRNA levels from TG and hypothalamus were analyzed by immunohistochemistry and real-time quantitative PCR. CGRP release from TG and dura mater were measured using an enzyme-linked immunosorbent assay. In addition, the vasomotor effect of progesterone on male and female basilar artery segments was investigated with myography. Results: Progesterone and progesterone receptor -A (PR-A) immunoreactivity were found in TG. Progesterone was located predominantly in cell membranes and in Aδ-fibers, and PR-A was found in neuronal cytoplasm and nucleus, and in satellite glial cells. The number of positive progesterone immunoreactive cells in the TG was higher in female compared to male rats. The PR mRNA was expressed in both hypothalamus and TG; however, the PR expression level was significantly higher in the hypothalamus. Progesterone did not induce a significant change neither in basal level nor upon stimulated release of CGRP from dura mater or TG in male or female rats when compared to the vehicle control. However, pre-treated with 10 µM progesterone weakly enhanced capsaicin induced CGRP release observed in the dura mater of male rats. Similarly, in male basilar arteries, progesterone significantly amplified the dilation in response to capsaicin. Conclusions: In conclusion, these results highlight the potential for progesterone to modulate sensory neurotransmission and vascular responses in a complex manner, with effects varying by sex, tissue type, and the nature of the stimulus. Further investigations are needed to elucidate the underlying mechanisms and physiological implications of these findings.
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| 7. |
- Rehnström, Mimmi, et al.
(författare)
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Ovariectomy Reduces Vasocontractile Responses of Rat Middle Cerebral Arteries After Focal Cerebral Ischemia
- 2022
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Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 79:1, s. 122-128
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Effects of sex hormones on stroke outcome are not fully understood. A deleterious consequence of cerebral ischemia is upregulation of vasoconstrictor receptors in cerebral arteries that exacerbate stroke injury. Here, we tested the hypothesis that female sex hormones alter vasocontractile responses after experimental stroke in vivo or after organ culture in vitro, a model of vasocontractile receptor upregulation. Female rats with intact ovaries and ovariectomized (OVX) females treated with 17β-estradiol, progesterone, or placebo were subjected to transient, unilateral middle cerebral artery occlusion followed by reperfusion (I/R). The maximum contractile response, measured my wire myography, in response to the endothelin B receptor agonist sarafotoxin 6c was increased in female arteries after I/R, but the maximum response was significantly lower in arteries from OVX females. Maximum contraction mediated by the serotonin agonist 5-carboxamidotryptamine was diminished after I/R, with arteries from OVX females showing a greater decrease in maximum contractile response. Contraction elicited by angiotensin II was similar in all arteries. Neither estrogen nor progesterone treatment of OVX females affected I/R-induced changes in endothelin B- and 5-carboxamidotryptamine-induced vasocontraction. These findings suggest that sex hormones do not directly influence vasocontractile alterations that occur after ischemic stroke; however, loss of ovarian function does impact this process.
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| 8. |
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| 9. |
- Bayrak Pehlivan, Ilknur, et al.
(författare)
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Electrochromic solar water splitting using a cathodic WO3 electrocatalyst
- 2021
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Ingår i: Nano Energy. - : Elsevier. - 2211-2855 .- 2211-3282. ; 81
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Tidskriftsartikel (refereegranskat)abstract
- Solar-driven water splitting is an emerging technology with high potential to generate fuel cleanly and sustainably. In this work, we show that WO3 can be used as a cathodic electrocatalyst in combination with (Ag,Cu) InGaSe2 solar cell modules to produce hydrogen and provide electrochromic functionality to water splitting devices. This electrochromic effect can be used to monitor the charge state or performance of the catalyst for process control or for controlling the temperature and absorbed heat due to tunable optical modulation of the electrocatalyst. WO3 films coated on Ni foam, using a wide range of different sputtering conditions, were investigated as cathodic electrocatalysts for the water splitting reaction. The solar-to-hydrogen (STH) efficiency of solar-driven water electrolysis was extracted using (Ag,Cu)InGaSe2 solar cell modules with a cell band gap varied in between 1.15 and 1.25 eV with WO3 on Ni foam-based electrolyzers and yielded up to 13% STH efficiency. Electrochromic properties during water electrolysis were characterized for the WO3 films on transparent substrate (indium tin oxide). Transmittance varied between 10% and 78% and the coloration efficiency at a wavelength of 528 nm and the overpotential of 400 mV was 40 cm(2) C-1. Hydrogen ion consumption in ion intercalation for electrochromic and hydrogen gas production for water electrolysis processes was discussed.
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| 10. |
- Bayrak Pehlivan, Ilknur, et al.
(författare)
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NiMoV and NiO-based catalysts for efficient solar-driven water splitting using thermally integrated photovoltaics in a scalable approach
- 2021
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Ingår i: iScience. - : Cell Press. - 2589-0042. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- In this work, a trimetallic NiMoV catalyst is developed for the hydrogen evolution reaction and characterized with respect to structure, valence, and elemental distribution. The overpotential to drive a 10 mA cm−2 current density is lowered from 94 to 78 mV versus reversible hydrogen electrode by introducing V into NiMo. A scalable stand-alone system for solar-driven water splitting was examined for a laboratory-scale device with 1.6 cm2 photovoltaic (PV) module area to an up-scaled device with 100 cm2 area. The NiMoV cathodic catalyst is combined with a NiO anode in alkaline electrolyzer unit thermally connected to synthesized (Ag,Cu) (In,Ga)Se2 ((A)CIGS) PV modules. Performance of 3- and 4-cell interconnected PV modules, electrolyzer, and hydrogen production of the PV electrolyzer are examined between 25°C and 50°C. The PV-electrolysis device having a 4-cell (A)CIGS under 100 mW cm−2 illumination and NiMoV-NiO electrolyzer shows 9.1% maximum and 8.5% averaged efficiency for 100 h operation.
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