Flow sensitivity of coronary endothelial luminal membrane G‐protein coupled receptors results from their lectinic nature

Extensive evidence shows that coronary endothelial luminal membrane (CELM) Lectins ( L ) and oligosaccharides ( O ) contribute to flow detection. Flow may induce a reversible L‐O complexing causing flow‐induced endothelial cardiac responses (FIER). HYPOTHESIS. O : endothelial glycocalyx oligosaccharide. L : a transmembrane Lectinic proteinParacrine endothelial cell signaling could result from either formation of O‐L or its dissociation into O and L . We have: 1) shown that O containing N‐Acetylglucosamine, Mannose and Galactose participate in FIER and 2) affinity resins containing these three sugars bind and isolate CELM's L . In contrast, CELM proteins like VCAM‐1, ICAM‐1, PECAM‐1 and βENaC are flow sensitive, while a series of G‐protein receptors (R): α 1 A‐R, AT 1 R, ETAR, PRL‐R, TXA 2 R, A 1 ‐R, A 2 A‐R and B 2 R, likely are flow sensitive. We hypothesized they are flow sensitive because they have L properties. In CELM's L fraction we performed Western Dot Blot for each of these proteins and all proteins were positively identified. They are L . Our hypothesis also implies; 1) flow activates/inhibit R, i. e. its hormone sensitivity is flow dependent and 2) the flow‐dependent hormone sensitivity of R is determined by presence or absence of O . In isolated perfused guinea pig hearts, these implications were explored for the vascular and inotropic effects of three hormones: Epinephrine (α 1 A‐R), Endothelin (ETAR) and Bradikinin (B 2 R). The dose‐response curves for these three hormones were flow dependent and this flow‐dependence was altered by Hyaluronidase and Heparinase. Our results establish that hormone sensitivity of CELM's G‐coupled R's is flow modulated because they are L coupled to O .