Prostanoid receptors: ontogeny and implications in vascular physiology

Prostanoids exert significant effects on circulatory beds. They play a role in the response of the vasculature to adjustments in perfusion pressure and oxygen and carbon dioxide tension, and they mediate the actions of numerous factors. The role of prostanoids in governing circulation of the perinate is suggested to surpass that in the adult. Prostanoids are abundantly generated in the perinate. They have been implicated in autoregulation of blood flow as studied in brain and eyes. Prostaglandins are also dominant regulators of ductus arteriosus tone. The effects of these autacoids are mediated through specific G protein-coupled receptors. In addition to the pharmacological characterization of the prostanoid receptors, important advances in understanding the biology of these receptors have been made in the last decade. Their cloning and the development of animals with disrupted genes of these receptors have been very informative. The involvement of prostanoid receptors in the developing subject, especially on brain and ocular vasculature and on ductus arteriosus, has also begun to be investigated; the expression of these receptors changes with development. Some but not all of the ontogenic changes in these receptors are attributed to homologous regulation. Interestingly, in the process of elucidating their effects, functional perinuclear prostaglandin E2receptors have been uncovered. This article reviews prostanoid receptors and addresses implications on the developing subject with attention to vascular physiology.

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Molecular and pharmacological characterization of genes encoding urotensin-II peptides and their cognate G-protein-coupled receptors from the mouse and monkey

British Journal of Pharmacology ◽

10.1038/sj.bjp.0704671 ◽

2002 ◽

Vol 136 (1) ◽

pp. 9-22 ◽

Cited By ~ 100

Author(s):

Nabil A. Elshourbagy ◽

Stephen A. Douglas ◽

Usman Shabon ◽

Stephen Harrison ◽

Graham Duddy ◽

...

Keyword(s):

G Protein ◽

G Protein Coupled Receptors ◽

Urotensin Ii ◽

Pharmacological Characterization ◽

Genes Encoding ◽

G Protein Coupled

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G-Protein Coupled Receptor-Evoked Glutamate Exocytosis from Astrocytes: Role of Prostaglandins

Neural Plasticity ◽

10.1155/2014/254574 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 10

Author(s):

Corrado Cali ◽

Jan Lopatar ◽

Francesco Petrelli ◽

Luca Pucci ◽

Paola Bezzi

Keyword(s):

G Protein ◽

Neutralizing Antibody ◽

Secretory Cells ◽

Prostaglandin E ◽

Specific Population ◽

Extracellular Release ◽

Pharmacological Blockade ◽

G Protein Coupled ◽

Cell Medium

Astrocytes are highly secretory cells, participating in rapid brain communication by releasing glutamate. Recent evidences have suggested that this process is largely mediated by Ca2+-dependent regulated exocytosis of VGLUT-positive vesicles. Here by taking advantage of VGLUT1-pHluorin and TIRF illumination, we characterized mechanisms of glutamate exocytosis evoked by endogenous transmitters (glutamate and ATP), which are known to stimulate Ca2+elevations in astrocytes. At first we characterized the VGLUT1-pHluorin expressing vesicles and found that VGLUT1-positive vesicles were a specific population of small synaptic-like microvesicles containing glutamate but which do not express VGLUT2. Endogenous mediators evoked a burst of exocytosis through activation of G-protein coupled receptors. Subsequent glutamate exocytosis was reduced by about 80% upon pharmacological blockade of the prostaglandin-forming enzyme, cyclooxygenase. On the other hand, receptor stimulation was accompanied by extracellular release of prostaglandin E2(PGE2). Interestingly, administration of exogenous PGE2producedper serapid, store-dependent burst exocytosis of glutamatergic vesicles in astrocytes. Finally, when PGE2-neutralizing antibody was added to cell medium, transmitter-evoked exocytosis was again significantly reduced (by about 50%). Overall these data indicate that cyclooxygenase products are responsible for a major component of glutamate exocytosis in astrocytes and that large part of such component is sustained by autocrine/paracrine action of PGE2.

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Deciphering the specific role of Gαi/o isoforms: functional selective oxytocin ligands and somatostatin SST5 receptor mutants

Biochemical Society Transactions ◽

10.1042/bst20120306 ◽

2013 ◽

Vol 41 (1) ◽

pp. 166-171 ◽

Cited By ~ 3

Author(s):

Marta Busnelli ◽

Erika Peverelli ◽

Giovanna Mantovani ◽

Anna Spada ◽

Bice Chini

Keyword(s):

Somatostatin Receptor ◽

Receptor Activation ◽

G Protein Coupled Receptors ◽

Receptor Coupling ◽

Biological Responses ◽

Selective Ligands ◽

Specific Effector ◽

G Protein Coupled

Receptor coupling to different G-proteins and β-arrestins has been described for a number of GPCRs (G-protein-coupled receptors), suggesting a multi-state model of receptor activation in which each receptor can assume a number of different active conformations, each capable of promoting the coupling to a specific effector. Consistently, functional-selective ligands and biased agonists have been described to be able to induce and/or stabilize only a subset of specific active conformations. Furthermore, GPCR mutants deficient in selective coupling have been reported. Functional selective ligands and receptor mutants thus constitute unique tools to dissect the specific roles of different effectors, in particular among the Gi/o family. In the present mini-review, we focus on (i) the identification of functional selective OXT (oxytocin)-derived peptides capable of activating single Gi/o isoforms, namely Gi1 or Gi3; and (ii) the characterization of an SS (somatostatin) receptor SST5 mutant selectively impaired in its GoA coupling. These analogues and receptor mutants represent unique tools for examining the contribution of Gi/o isoforms in complex biological responses and open the way for the development of drugs with peculiar selectivity profiles.

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The complex role of Prostaglandin E2-EP receptor signaling in wound healing

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00185.2020 ◽

2020 ◽

Author(s):

Kristy E. Gilman ◽

Kirsten H. Limesand

Keyword(s):

Wound Healing ◽

G Protein ◽

Lipid Mediators ◽

G Protein Coupled Receptors ◽

Prostaglandin E ◽

Receptor Signaling ◽

Wound Healing Response ◽

Ep Receptor ◽

G Protein Coupled

Prostaglandins are critical lipid mediators involved in the wound healing response, with prostaglandin E2 (PGE2) being the most complex and exhibiting the most diverse physiological outputs. PGE2 signals via four G-protein coupled receptors, termed EP-receptors 1-4, that induce distinct signaling pathways upon activation and lead to an array of different outputs. Recent studies examining the role of PGE2 and EP receptor signaling in wound healing following various forms of tissue damage are discussed in this review.

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Platelet Function and Therapeutic Applications in Dogs: Current Status and Future Prospects

Animals ◽

10.3390/ani10020201 ◽

2020 ◽

Vol 10 (2) ◽

pp. 201

Author(s):

Laura Cortese ◽

Pete W. Christopherson ◽

Alessandra Pelagalli

Keyword(s):

Platelet Function ◽

Platelet Rich Plasma ◽

Functional Characterization ◽

Current Status ◽

Significant Progress ◽

Therapeutic Benefits ◽

Platelet Structure ◽

Made In

Significant progress has been made in the functional characterization of canine platelets in the last two decades. The role of canine platelets in hemostasis includes their adhesion to the subendothelium, activation, and aggregation, leading to primary clot formation at the site of injury. Studies on canine platelet function and advancements in laboratory testing have improved the diagnosis and understanding of platelet-related disorders as well as the knowledge of the mechanisms behind these diseases. This review focuses on the most recent discoveries in canine platelet structure, function, and disorders; and discusses the efficacy of various tests in the diagnosis of platelet-related disorders. With the relatively recent discovery of angiogenetic and reparative effects of growth factors found in platelets, this review also summarizes the use of canine platelet-rich plasma (PRP) alone or in association with stem cells in regenerative therapy. The characterization of proteomic and lipidomic profiles and development of platelet gene therapy in veterinary species are areas of future study with potential for major therapeutic benefits.

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Role of LPXRFamide peptide in the neuroendocrine regulation of reproduction in fish

Open Life Sciences ◽

10.2478/s11535-011-0048-2 ◽

2011 ◽

Vol 6 (5) ◽

pp. 853-860 ◽

Cited By ~ 1

Author(s):

Md. Shahjahan ◽

Hironori Ando

Keyword(s):

Gonadal Development ◽

Gonadotropin Releasing Hormone ◽

Fish Reproduction ◽

Lower Vertebrates ◽

Hypothalamic Control ◽

G Protein Coupled ◽

Made In

AbstractThe decapeptide gonadotropin-releasing hormone (GnRH) is the primary factor responsible for the hypothalamic control of gonadotropin (GTH) secretion. This review focuses on a family of neuropeptides, LPXRFamide (LPXRFa) peptides, which have been implicated in the regulation of GTH secretion. LPXRFa acts on the pituitary via a G protein-coupled receptor, LPXRFa-R, to enhance gonadal development and maintenance by increasing gonadotropin release and synthesis. Because LPXRFa exists and functions in several fish species, LPXRFa is considered to be a key neurohormone in fish reproduction control. The precursors to LPXRFamide peptides encoded plural LPXRFamide peptides and were highly divergent in vertebrates, particularly in lower vertebrates. Tissue distribution analyses indicated that LPXRFamide peptides were highly concentrated in the hypothalamus and other brainstem regions. In view of the localization and expression of LPXRFamide peptides in the hypothalamo-hypophysial system, LPXRFamide peptide in fish increase GTH release in vitro and in vivo. This review summarizes the advances made in our understanding of the biosynthesis, mode of action and functional significance of LPXRFa, a newly discovered key neurohormone.

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Pharmacological Characterization of Sephadex-lnduced Oedema in Rat Paws: Predominant Role of Serotonin and Platelet-Activating Factor

International Archives of Allergy and Immunology ◽

10.1159/000237269 ◽

1996 ◽

Vol 109 (4) ◽

pp. 398-406 ◽

Cited By ~ 7

Author(s):

Janetti N. Francischi ◽

Murilo F. Dias ◽

Orivaldo A. Rocha ◽

Maria S. de Abreu Castro ◽

Maria A. Kiyomi Funayama Tatsuo ◽

...

Keyword(s):

Platelet Activating Factor ◽

Predominant Role ◽

Pharmacological Characterization

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Pharmacological Characterization of an Adenylyl Cyclase-Coupled 5-HT Receptor in Aplysia: Comparison With Mammalian 5-HT Receptors

Journal of Neurophysiology ◽

10.1152/jn.01004.2002 ◽

2003 ◽

Vol 89 (3) ◽

pp. 1440-1455 ◽

Cited By ~ 22

Author(s):

Jonathan E. Cohen ◽

Chiadi U. Onyike ◽

Virginia L. McElroy ◽

Allison H. Lin ◽

Thomas W. Abrams

Keyword(s):

Adenylyl Cyclase ◽

Rank Order ◽

Physiological Saline ◽

Receptor Subtypes ◽

Pharmacological Profile ◽

Pharmacological Characterization ◽

Firing Properties ◽

Stimulation Of

We attempted to identify compounds that are effective in blocking the serotonin (5-hydroxytryptamine, 5-HT) receptor(s) that activate adenylyl cyclase (AC) in Aplysia CNS. We call this class of receptor 5-HTapAC. Eight of the 14 antagonists tested were effective against 5-HTapAC in CNS membranes with the following rank order of potency: methiothepin > metergoline ∼ fluphenazine > clozapine > cyproheptadine ∼ risperidone ∼ ritanserin > NAN-190. GR-113808, olanzapine, Ro-04-6790, RS-102221, SB-204070, and spiperone were inactive. Methiothepin completely blocked 5-HT stimulation of AC with a K b of 18 nM. Comparison of the pharmacological profile of the 5-HTapAC receptor with those of mammalian 5-HT receptor subtypes suggested it most closely resembles the 5-HT6 receptor. AC stimulation in Aplysia sensory neuron (SN) membranes was also blocked by methiothepin. Methiothepin substantially inhibited two effects of 5-HT on SN firing properties that are mediated by a cAMP-dependent reduction in S-K+ current: spike broadening in tetraethylammonium/nifedipine and increased excitability. Consistent with cyproheptadine blocking 5-HT stimulation of AC, cyproheptadine also blocked the 5-HT-induced increase in SN excitability. Methiothepin was less effective in blocking AC-mediated modulatory effects of 5-HT in electrophysiological experiments on SNs than in blocking AC stimulation in CNS or SN membranes. This reduction in potency appears to be due to effects of the high ionic strength of physiological saline on the binding of this antagonist to the receptor. Methiothepin also antagonized AC-coupled dopamine receptors but not AC-coupled small cardioactive peptide receptors. In conjunction with other pharmacological probes, this antagonist should be useful in analyzing the role of 5-HT in various forms of neuromodulation in Aplysia.

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Involvement of intramural prostaglandin E2 in prenatal patency of the lamb ductus arteriosus

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y86-124 ◽

1986 ◽

Vol 64 (6) ◽

pp. 737-744 ◽

Cited By ~ 34

Author(s):

Flavio Coceani ◽

Dayle Huhtanen ◽

Nancy C. Hamilton ◽

Isis Bishai ◽

Peter M. Olley

Keyword(s):

Release Rate ◽

Enzyme System ◽

Reduced Glutathione ◽

Ductus Arteriosus ◽

Prostaglandin E ◽

Concomitant Treatment ◽

Contractile State ◽

Wet Weight ◽

Near Term

Release of prostaglandin E2 (PGE2) was studied in isolated ductus arteriosus preparations from immature (103 or 104 days gestation; term, 147 days) and near-term fetal lambs. Mature preparations produced measurable amounts of the compound in most cases and the release rate was 19 ± 2 pg/(100 mg wet weight∙min) at a [Formula: see text] of 3–8 Torr (1 Torr = 133.3 Pa). PGE2 release increased with the [Formula: see text] of the medium, peak values (about 125 pg/(100 mg∙min)) being attained at 106–276 Torr when the oxygen-induced contraction was still submaximal. Experiments in which tissues were either contracted with excess potassium or relaxed with CO proved that PGE2 formation is independent from the contractile state. PGE2 was also released from ductus preparations lacking the adventitia, the intima, or both; however, release values were maximal when the adventitia was preserved. The magnitude of the intrinsic tone in these stripped preparations was inversely related to the rate of PGE2 formation. Reduced glutathione increased PGE2 release from the mature ductus, whole or stripped, and also relaxed hypoxic preparations; both effects were reversed by concomitant treatment with indomethacin. PGE2 synthesis tended to be greater in the immature than the mature ductus, maximal values (115 ± 27 pg/(100 mg∙min)) being observed at 6–8 Torr. We conclude that the ductus arteriosus is endowed with an enzyme system for the synthesis of PGE2 whose function accords with an effector role of the compound in the regulation of tone. These findings, together with the potent relaxation exerted by PGE2 at low [Formula: see text], indicate that the locally generated prostaglandin is well suited for keeping the ductus patent in the fetus.

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