scholarly journals Optogenetic manipulation of cGMP highlights PDE5 as the predominant cGMP-hydrolyzing PDE in megakaryocytes

2021 ◽  
Author(s):  
Yujing Zhang ◽  
Pascal Benz ◽  
Daniel Stehle ◽  
Shang Yang ◽  
Hendrikje Kurz ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Types ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Pde5 Inhibition ◽  
Cgmp Signalling ◽  
Spatiotemporal Regulation ◽  
Blastocladiella Emersonii ◽  
First Time ◽  
Platelet Formation

Cyclic guanosine monophosphate (cGMP) signalling plays a fundamental role in many cell types including platelets. cGMP has been implicated in platelet formation, but mechanistic detail about its spatiotemporal regulation in megakaryocytes (MKs) is lacking. We expressed a photo-activated guanylyl cyclase, Blastocladiella emersonii Cyclase opsin (BeCyclop), after viral-mediated gene transfer in bone marrow (BM)-derived MKs to precisely light-modulate cGMP levels. BeCyclop-MKs showed a significantly increased cGMP concentration after illumination, which was strongly dependent on phosphodiesterase (PDE) 5 activity. This finding was corroborated by real-time imaging of cGMP signals which revealed that pharmacological PDE5 inhibition also potentiated nitric oxide (NO) triggered cGMP generation in BM MKs. In summary, we established for the first time optogenetics in primary MKs and identified PDE5 as the predominant PDE regulating cGMP levels in MKs. These findings also demonstrate that optogenetics allows for the precise manipulation of MK biology.

Carbon monoxide may be an important molecule in migraine and other headaches

Cephalalgia ◽  
2014 ◽  
Vol 34 (14) ◽  
pp. 1169-1180 ◽  
Author(s):  
Nanna Arngrim ◽  
Henrik W Schytz ◽  
Mette K Hauge ◽  
Messoud Ashina ◽  
Jes Olesen
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Biological Processes ◽  
Recent Information ◽  
Signalling Molecule ◽  
Nociceptive Processing ◽  
First Time ◽  
Arterial Tone

Introduction Carbon monoxide was previously considered to just be a toxic gas. A wealth of recent information has, however, shown that it is also an important endogenously produced signalling molecule involved in multiple biological processes. Endogenously produced carbon monoxide may thus play an important role in nociceptive processing and in regulation of cerebral arterial tone. Discussion Carbon monoxide-induced headache shares many characteristics with migraine and other headaches. The mechanisms whereby carbon monoxide causes headache may include hypoxia, nitric oxide signalling and activation of cyclic guanosine monophosphate pathways. Here, we review the literature about carbon monoxide-induced headache and its possible mechanisms. Conclusion We suggest, for the first time, that carbon monoxide may play an important role in the mechanisms of migraine and other headaches.

scholarly journals Cyclic Guanosine Monophosphate Modulates Locomotor Acceleration Induced by Nitric Oxide but not Serotonin in Clione limacina Central Pattern Generator Swim Interneurons

2020 ◽  
Author(s):  
Thomas J Pirtle ◽  
Richard A Satterlie
Keyword(s):  
Nitric Oxide ◽  
Central Pattern Generator ◽  
Guanylyl Cyclase ◽  
Signal Transduction Pathway ◽  
Soluble Guanylyl Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Pattern Generator ◽  
Guanosine Monophosphate ◽  
Cellular Changes ◽  
Clione Limacina

Abstract Typically, the marine mollusk, Clione limacina, exhibits a slow, hovering locomotor gait to maintain its position in the water column. However, the animal exhibits behaviorally relevant locomotor swim acceleration during escape response and feeding behavior. Both nitric oxide and serotonin mediate this behavioral swim acceleration. In this study, we examine the role that the second messenger, cGMP, plays in mediating nitric oxide and serotonin-induced swim acceleration. We observed that the application of an analog of cGMP or an activator of soluble guanylyl cyclase increased fictive locomotor speed recorded from Pd-7 interneurons of the animal’s locomotor central pattern generator. Moreover, inhibition of soluble guanylyl cyclase decreased fictive locomotor speed. These results suggest that basal levels of cGMP are important for slow swimming and that increased production of cGMP mediates swim acceleration in Clione. Because nitric oxide has its effect through cGMP signaling and because we show herein that cGMP produces cellular changes in Clione swim interneurons that are consistent with cellular changes produced by serotonin application, we hypothesize that both nitric oxide and serotonin function via a common signal transduction pathway that involves cGMP. Our results show that cGMP mediates nitric oxide-induced but not serotonin-induced swim acceleration in Clione.

The nitric oxide–cGMP signaling pathway plays a significant role in tolerance to the analgesic effect of morphine

2011 ◽  
Vol 89 (2) ◽  
pp. 89-95 ◽  
Author(s):  
Ercan Ozdemir ◽  
Ihsan Bagcivan ◽  
Nedim Durmus ◽  
Ahmet Altun ◽  
Sinan Gursoy
Keyword(s):  
Nitric Oxide ◽  
Analgesic Effect ◽  
Soluble Guanylate Cyclase ◽  
Morphine Tolerance ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Albino Rats ◽  
Tail Flick ◽  
Analgesic Effects ◽  
Cgmp Signaling

Although the phenomenon of opioid tolerance has been widely investigated, neither opioid nor nonopioid mechanisms are completely understood. The aim of the present study was to investigate the role of the nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) pathway in the development of morphine-induced analgesia tolerance. The study was carried out on male Wistar albino rats (weighing 180–210 g; n = 126). To develop morphine tolerance, animals were given morphine (50 mg/kg; s.c.) once daily for 3 days. After the last dose of morphine was injected on day 4, morphine tolerance was evaluated. The analgesic effects of 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1), BAY 41-2272, S-nitroso-N-acetylpenicillamine (SNAP), NG-nitro-l-arginine methyl ester (L-NAME), and morphine were considered at 15 or 30 min intervals (0, 15, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests (n = 6 in each study group). The results showed that YC-1 and BAY 41-2272, a NO-independent activator of soluble guanylate cyclase (sGC), significantly increased the development and expression of morphine tolerance, and L-NAME, a NO synthase (NOS) inhibitor, significantly decreased the development of morphine tolerance. In conclusion, these data demonstrate that the nitric oxide–cGMP signal pathway plays a pivotal role in developing tolerance to the analgesic effect of morphine.

Nitric Oxide/Cyclic Guanosine Monophosphate Signalling Mediates an Inhibitory Action on Sensory Pathways of the Micturition Reflex in the Rat

2010 ◽  
Vol 58 (4) ◽  
pp. 616-625 ◽  
Author(s):  
Romain Caremel ◽  
Stephanie Oger-Roussel ◽  
Delphine Behr-Roussel ◽  
Philippe Grise ◽  
François A. Giuliano
Keyword(s):  
Nitric Oxide ◽  
Inhibitory Action ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Micturition Reflex ◽  
Sensory Pathways

Distinct regulation of nitric oxide and cyclic guanosine monophosphate production by steroid hormones in the rat uterus

2000 ◽  
Vol 6 (5) ◽  
pp. 404-414 ◽  
Author(s):  
Irina A. Buhimschi ◽  
Chandreskar Yallampalli ◽  
Catalin S. Buhimschi ◽  
George R. Saade ◽  
Robert E. Garfield
Keyword(s):  
Nitric Oxide ◽  
Steroid Hormones ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Rat Uterus

scholarly journals Nitric Oxide

2007 ◽  
Vol 107 (5) ◽  
pp. 822-842 ◽  
Author(s):  
Noboru Toda ◽  
Hiroshi Toda ◽  
Yoshio Hatano ◽  
David C. Warltier
Keyword(s):  
Nitric Oxide ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Nitric Oxide Release ◽  
Blood Flows ◽  
Anesthetic Agents ◽  
Regional Blood Flows ◽  
Peripheral Arterial

There has been an explosive increase in the amount of interesting information about the physiologic and pathophysiologic roles of nitric oxide in cardiovascular, nervous, and immune systems. The possible involvement of the nitric oxide-cyclic guanosine monophosphate pathway in the effects of anesthetic agents has been the focus of many investigators. Relaxations of cerebral and peripheral arterial smooth muscle as well as increases in cerebral and other regional blood flows induced by anesthetic agents are mediated mainly via nitric oxide released from the endothelium and/or the nitrergic nerve and also via prostaglandin I2 or endothelium-derived hyperpolarizing factor. Preconditioning with volatile anesthetics protects against ischemia-reperfusion-induced myocardial dysfunction and cell death or neurotoxicity, possibly through nitric oxide release. Inhibition of nitric oxide synthase decreases the anesthetic requirement. Involvement of nitric oxide in the effects of volatile, intravenous, and local anesthetics differs. This review article includes a summary of information about the sites and mechanisms by which various anesthetic agents interact with the nitric oxide-cyclic guanosine monophosphate system.

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