Pharmacology of Serotonin Receptors Causing Contraction of Isolated Bovine Posterior Ciliary Arteries: Role in Ocular Blood Flow

Njie‐Mbye, Ya Fatou; Robinson, Jenaye; Mitchell-Bush, Leah; McKoy, Marshalyn G.; Opere, Catherine A.; Ohia, Sunny E.; Sharif, Naj

doi:10.1089/jop.2017.0124

Cited by 7 publications

(5 citation statements)

References 21 publications

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“…A recent article, published by Njie-Mbye et al, 2018, showed that 5-HT 2 agonists (5-HT 2A , 5-HT 2B , 5-HT 2C ) produced VC that can be antagonized by 5-HT 2 receptor blockers. 5-HT 1 receptor agonists did not produce vasoconstrictor eff ect in vitro 30 .…”

Section: Rolesmentioning

confidence: 82%

The Role of Histamine and Serotonin in the Control of Vascular Motricity of the Anterior Ocular Segment - Review of the Literature from 1997 to 2018

Lunca¹,

Păunescu²,

Coman³

et al. 2018

Rev. Med. Mod.

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Histamine and serotonin, besides known systemic effects, can influence vascular tone at the eye level. The review of the literature from 1997 to 2018 suggests that these ocular effects are very variable -both vasodilation and vasoconstriction. Specifi c agonists or antagonists acting in the histamine and serotonin domains, are probably more useful than endogenous substances as working tools for discovering the functional elements involved in regulating ocular vascular tone. Knowing that intraocular pressure regulation also depends on the vascular tone of the anterior ocular segment, some of the substances under review may be candidates for potential intraocular pressure lowering drugs. RezumatHistamina și serotonina, pe lângă efectele sistemice cunoscute, pot influenţa tonusul vascular de la nivel ocular. Recenzia literaturii de specialitate din perioada 1997-2018 a arătat că aceste efecte oculare sunt foarte variabileatât vasodilataţie, cât și vasoconstricţie. Substanţele care modulează la nivel de receptor aceste efecte (agoniștii și antagoniștii histaminergici și serotoninergici) sunt probabil mai utili decât substanţele endogene ca instrumente de lucru pentru descoperirea elementelor funcţionale implicate în reglarea tonusului vascular ocular. Cunoscând că reglarea presiunii intraoculare depinde și de tonusul vascular al segmentului anterior ocular, unele din substanţele recenzate ar putea prezenta și efecte hipotonizante oculare.

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Section: Rolesmentioning

confidence: 82%

The Role of Histamine and Serotonin in the Control of Vascular Motricity of the Anterior Ocular Segment - Review of the Literature from 1997 to 2018

Lunca¹,

Păunescu²,

Coman³

et al. 2018

Rev. Med. Mod.

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“…Human and/or non-human primate ocular cells and tissues, or cells expressing human cloned receptors or enzymes, should be used whenever possible, to have appropriate linkage to the human disease Sharif, 2020a;Sharif, 2020b). Ideally, isolated and well characterized human CM (Sharif et al, 2003a), TM (Sharif et al, 2003b; and NPCE ) cells, or bovine TM cells (Mao et al, 2012), or strips of human/animal ocular tissues (Wiederholt et al, 2000;Rosenthal et al, 2005;Ohia et al, 2018;Njie-Mbye et al, 2018) or ex-vivo models (e.g., Sharif et al, 2009;Sharif et al, 2014b) should be used for testing and characterizing ocular hypotensive compounds. If this is not possible, then suitable higher order species-derived cells and tissues may suffice including those from bovine, porcine and non-human primate sources.…”

Section: Assays and Techniques Used For Screening Of Potential Ocular Hypotensive Compoundsmentioning

confidence: 99%

“…Functional read-outs from cultured cells in multiwell plates used to determine such quantifiable activity are second messengers (e.g., cAMP (Crider et al, 1998;Crider et al, 2000)/ cGMP (Dismuke et al, 2009;Katoli et al, 2010)); inositol phosphates accumulation (Sharif and Xu, 1999;Griffin et al, 1997;Griffin et al, 1998;Sharif et al, 1998)/intracellular Ca 2+ ([Ca 2+ ] i ) mobilization (Griffin et al, 1997;Griffin et al, 1998;Kelly et al, 2003) (Figure 16A), or enzyme release and activation Sharif et al, 2014a;Sharif et al, 2016), or cell contraction/relaxation by in-gel assays (Ramachandran et al, 2011) or by electrical resistance measurements Vollmer et al, 2020), or cell volume change (Patil et al, 2016;Dismuke et al, 2009;Dismuke et al, 2010). Tissue samples mounted in organ-baths (e.g., iris sphincter muscle; Sharif et al, 2008), rat uterus strips (Sharif, 2008) or bovine ciliary muscle/ arteries (Njie-Mbye et al, 2018;Ohia et al, 2018) or human TM strips (Wiederholt et al, 2000) can provide functional read-outs of contraction or relaxation which can be quantified and test compounds rank ordered according to their relative potencies and intrinsic activities/maximal efficacies. For example, travoprost acid (TA) most potently contracted cat iris strips compared to all the other FP-receptor PG agonists tested, and TA was also a full agonist relative to the other compounds tested which clearly behaved as partial agonists in this assay system (Sharif et al, 2008).…”

Section: Assays and Techniques Used For Screening Of Potential Ocular Hypotensive Compoundsmentioning

confidence: 99%

Therapeutic Drugs and Devices for Tackling Ocular Hypertension and Glaucoma, and Need for Neuroprotection and Cytoprotective Therapies

Sharif

2021

Front. Pharmacol.

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Damage to the optic nerve and the death of associated retinal ganglion cells (RGCs) by elevated intraocular pressure (IOP), also known as glaucoma, is responsible for visual impairment and blindness in millions of people worldwide. The ocular hypertension (OHT) and the deleterious mechanical forces it exerts at the back of the eye, at the level of the optic nerve head/optic disc and lamina cribosa, is the only modifiable risk factor associated with glaucoma that can be treated. The elevated IOP occurs due to the inability of accumulated aqueous humor (AQH) to egress from the anterior chamber of the eye due to occlusion of the major outflow pathway, the trabecular meshwork (TM) and Schlemm’s canal (SC). Several different classes of pharmaceutical agents, surgical techniques and implantable devices have been developed to lower and control IOP. First-line drugs to promote AQH outflow via the uveoscleral outflow pathway include FP-receptor prostaglandin (PG) agonists (e.g., latanoprost, travoprost and tafluprost) and a novel non-PG EP2-receptor agonist (omidenepag isopropyl, Eybelis®). TM/SC outflow enhancing drugs are also effective ocular hypotensive agents (e.g., rho kinase inhibitors like ripasudil and netarsudil; and latanoprostene bunod, a conjugate of a nitric oxide donor and latanoprost). One of the most effective anterior chamber AQH microshunt devices is the Preserflo® microshunt which can lower IOP down to 10–13 mmHg. Other IOP-lowering drugs and devices on the horizon will be also discussed. Additionally, since elevated IOP is only one of many risk factors for development of glaucomatous optic neuropathy, a treatise of the role of inflammatory neurodegeneration of the optic nerve and retinal ganglion cells and appropriate neuroprotective strategies to mitigate this disease will also be reviewed and discussed.

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“…The team successfully ruled out several receptor classes and zoned in on the 5-HT 2 receptor family . We patented certain novel serotonergic compounds that were potent and efficacious ocular hypotensives with IOP-lowering up to 30% or greater in the OHT eyes of conscious Cynomolgus monkeys − and published several patents and papers − describing our efforts to lead the field and inspire other researchers to join the hunt for novel and efficacious drugs to treat OHT/POAG. Lessons learnt from the PG drug discovery programs helped us stay focused and we successfully established in-house receptor binding, cell-based functional assays and deployed the in vivo models to rapidly screen compounds that medicinal chemists synthesized.…”

Section: Challenges and Strategies To Discover Novel Drugs To Treat O...mentioning

confidence: 99%

Discovery to Launch of Anti-allergy (Emadine; Patanol/Pataday/Pazeo) and Anti-glaucoma (Travatan; Simbrinza) Ocular Drugs, and Generation of Novel Pharmacological Tools Such as AL-8810

Sharif

2020

ACS Pharmacol. Transl. Sci.

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The eye and eyesight are exquistly designed and are precious, and yet we often take them for granted. Good vision is critical for our long-term survival and for humanity's enduring progress. Unfortunately, since ocular diseases do not culminate in lifeand-death scenarios, awareness of the plight of millions of people suffering from such eye ailments is not publicized as other diseases. However, losing eyesight or falling victim to visual impairment is a frightening outlook for most people. Glaucoma, a collection of chronic optic neuropathies, of which the most prevalent form, primary open-angle glaucoma (POAG), is the second leading cause of irreversible blindness. POAG currently afflicts >70 million people worldwide and is an insidious, progressive, silent thief of sight that is asymptomatic. On the other hand, allergic conjunctivitis (AC), and the associated rhinitis ("hay-fever"), frequently victimizes a huge number of people worldwide, especially during seasonal changes. While not life-threatening, sufferers of AC soon learn the value of drugs to treat their signs and symptoms of AC as they desire rapid relief to overcome the ocular itching/pain, redness, and tearing AC causes. Herein, I will describe the collective efforts of many researchers whose industrious, diligent, and dedicated team work resulted in the discovery, biochemical/ pharmacological characterization, development and eventual launch of drugs to treat AC (e.g., olopatadine [Patanol/Pataday/Pazeo] and emedastine [Emedine]), and for treating ocular hypertension and POAG (e.g., travoprost [Travatan ] and Simbrinza). This represents a personal perspective.

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Pharmacology of Serotonin Receptors Causing Contraction of Isolated Bovine Posterior Ciliary Arteries: Role in Ocular Blood Flow

Cited by 7 publications

References 21 publications

The Role of Histamine and Serotonin in the Control of Vascular Motricity of the Anterior Ocular Segment - Review of the Literature from 1997 to 2018

The Role of Histamine and Serotonin in the Control of Vascular Motricity of the Anterior Ocular Segment - Review of the Literature from 1997 to 2018

Therapeutic Drugs and Devices for Tackling Ocular Hypertension and Glaucoma, and Need for Neuroprotection and Cytoprotective Therapies

Discovery to Launch of Anti-allergy (Emadine; Patanol/Pataday/Pazeo) and Anti-glaucoma (Travatan; Simbrinza) Ocular Drugs, and Generation of Novel Pharmacological Tools Such as AL-8810

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