The coronary endothelium behaves as a functional diffusion barrier for intravascular Angiotensin II

Rubio, Rafael; Torres-Tirado, David; Castillo-Hernández, Jesús; Chi‐Ahumada, Erika; Ramiro-Diaz, Juan Manuel; Knabb, Maureen

doi:10.1016/j.vph.2012.06.006

Cited by 4 publications

(9 citation statements)

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“…Among the increasing list of GPCR mechanosensors are the angiotensin II (AT 1 ), bradykinin (B 2 ), histamine (H 1 ), vasopressin (V 1A ), muscarinic (M 5 ), and endothelin (ET A ) receptors (2,9,33,36,62). These six GPCRs are found in the LESL (8,42,43,61). In this report, we demonstrate that these six LESL GPCRs plus another four GPCRs as well as the insulin receptor are lectinic.…”

mentioning

confidence: 64%

“…Thus our results with these sugar polymers demonstrate both in vitro isolation of LESL lectins and in situ differential binding to functional LESL signaling lectins that serve as flow sensors. These flow sensors are capable of inducing endothelial paracrine secretion, similar to a GPCR when agonist activated (6,8,42,43,61). The fact that a given flow-induced function can be experimentally and independently modulated from other functions supports the existence of multiple LESL flow-sensing structures (22,33,35).…”

Section: Discussionmentioning

confidence: 92%

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G protein-coupled receptors mediate coronary flow- and agonist-induced responses via lectin-oligosaccharide interactions

Perez-Aguilar

Torres-Tirado

Martell-Gallegos

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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Blood flow acts parallel to the coronary luminal endothelial surface layer (LESL) and modulates multiple parenchymal functions via the release of paracrine agents. Evidence indicates that the LESL may be a flow-sensing organelle and that perhaps through flow-induced lectin (L)·oligosaccharide (O) complex formation (L·O) participates in this process. LESL integrins and selectins are both lectinic and flow sensitive, but the L properties of flow-sensitive G protein-coupled receptors (GPCRs) are unknown. Therefore, we investigated the presence of L in the LESL and hypothesized that if flow-sensitive GPCRs are L, flow and O will determine their response to receptor activation. The LESL protein fraction isolated from guinea pig hearts was passed through an affinity chromatography column made of three sugars, mannose, galactose, and N-acetylglucosamine, and the lectinic fraction was eluted. Immune dot blot was used to identify L proteins in the LESL fraction. Our results indicate the following. 1) Two-dimensional SDS-PAGE (2D-SDS-PAGE) of the LESL lectinic fraction revealed at least 167 Ls. 2) Among these Ls, we identified three selectins and the GPCRs: angiotensin II, bradykinin (B2-R), adenosine A1 and A2, prolactin, endothelin, α1-adrenergic (α1A-R), thromboxane A2, β1-adrenergic, β3-adrenergic, and insulin receptors; the first six GPCRs are known to be flow sensitive. 3) The amplitude of receptor-induced vascular responses by α1A-R and B2-R activation (phenylephrine or bradykinin, respectively) was a function of flow and O (hyaluronidate). Our results support a novel mechanism of GPCR-mediated responses to flow via L·O interaction.

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confidence: 64%

Section: Discussionmentioning

confidence: 92%

G protein-coupled receptors mediate coronary flow- and agonist-induced responses via lectin-oligosaccharide interactions

Perez-Aguilar

Torres-Tirado

Martell-Gallegos

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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“…Receptor-proteins for several hormones are present in the endothelial luminal membrane. Moreover, in the luminal endothelial membrane, the presence of at least fourteen receptor-proteins has been established: Angiotensin AT1 and AT2, insulin, endothelin, prolactin, vasopressin, thromboxane A2, adenosine A1, A2, and A3, bradykinin, adrenergic α, β1, and β3 are present [12]- [14], [17], [43]- [45]. Fig.…”

Section: ) the Endothelial Luminal Membrane Of Many Organs Can Be Reliably Isolatedmentioning

confidence: 99%

“…Upon acting on its receptor, an agonist triggers two mechanisms: receptor activation and its internalization [12], [17], [18], [46]- [50]. During sustained agonist administration, the receptor membrane density gradually decreases, internalization.…”

Section: ) Agonist and Its Large Size-agonist When Intravascularly Administered Together At The Receptor Site Compete With Each Othermentioning

confidence: 99%

“…The two agonists, Ang II and Ang II-polymer (Ang-Pol), activate the luminal endothelial receptor equally. However, each agonist induces a quantitatively distinct receptor internalization and desensitization [12], [13], [17], [18]. Desensitization is rapid for Ang II and slow for the Ang II polymer.…”

Section: ) Agonist and Its Large Size-agonist When Intravascularly Administered Together At The Receptor Site Compete With Each Othermentioning

confidence: 99%

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The Endothelial Barrier Restricts Endocrine Actions to the Luminal Vascular Receptors: Changing the Paradigm: A Didactic Approach

Rubio

2021

EJMED

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In 1849, the first list of endocrine hormones was discovered and proposed that the synthesizing gland delivers it to the circulation. The circulatory hormone reaches the target organ, physically unimpeded acts directly on the parenchymal cells. Such a simplistic view persists despite new knowledge of an endothelial wall barrier and implications for every parenchymal cell in the body. This misconception leads to inadequate interpretations of data, wrong diagnosis and therapeutic expectations, erroneous hypotheses, and misleads further research work. The quest of this review is to play down this misconception by pointing out key overlooked findings of the vascular endothelial wall: 1) The selective endothelial barrier physically separates two same-hormone-containing compartments; the endocrine and the interstitial autocrine hormone compartments, 2) the hormone concentrations values in these compartments are independent of each other, 3) in each compartment the hormone acts solely on the receptors of that particular compartment, 4) multiple intravascular endocrine hormones act solely on their corresponding luminal endothelial membrane receptor (LEMR), without directly acting on the parenchymal cells, 5) Agonist-activation of LEMR triggers the release of specific paracrine endothelial agents that in conjunction with autocrine interstitial hormone modulate parenchymal function(s) and perhaps the turnover of the interstitial autocrine hormone, 6) these hormone compartments, functionally interact via paracrine exchange signaling, and the integrated intercourse of all these events result in the final hormonal organ effect. The present challenges to achieving more rationale therapeutic effects are to design agonists or antagonists that exclusively gain access to a target compartment and have high specificity for the receptor of the cells in that compartment.

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Molecular weight of different angiotensin II polymers directly determines: Density of endothelial membrane AT1 receptors and coronary vasoconstriction

Torres-Tirado

Ramiro-Diaz

Knabb

et al. 2013

Vascular Pharmacology

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The coronary endothelium behaves as a functional diffusion barrier for intravascular Angiotensin II

Cited by 4 publications

References 44 publications

G protein-coupled receptors mediate coronary flow- and agonist-induced responses via lectin-oligosaccharide interactions

G protein-coupled receptors mediate coronary flow- and agonist-induced responses via lectin-oligosaccharide interactions

The Endothelial Barrier Restricts Endocrine Actions to the Luminal Vascular Receptors: Changing the Paradigm: A Didactic Approach

Molecular weight of different angiotensin II polymers directly determines: Density of endothelial membrane AT1 receptors and coronary vasoconstriction

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