Investigation of the Presence and Distribution of Piezo-1 and GPR-4 Hemodynamic Receptors on the Internal and External Endothelial Surfaces of the Cavernous Segment of the Internal Carotid Artery.

Yener M. D. (Executive), Öztürk A., Çabuk B., Çolak T., Yener Y., Yazır Y.

TUBITAK Project, 1002 - Quick Support Program, 2025 - 2025

Project Type: TUBITAK Project
Support Program: 1002 - Quick Support Program
Begin Date: April 2025
End Date: October 2025

Project Abstract

The internal carotid artery (ICA) is a major component of the circulus arteriosus cerebri (Willis polygon) and supplies the principal arterial inflow to the brain. Before entering the intracranial compartment, the ICA passes through the cavernous sinus, a venous structure responsible for draining blood from the brain. In this segment, the artery displays a unique morphology: both its luminal surface and its external surface-directly exposed to venous blood-are covered by an endothelial layer, a distinctive histological feature not seen in typical muscular arteries. This unusual configuration suggests that the external surface of the cavernous segment may harbor vascular signal-sensing receptors contributing to cerebral hemodynamic feedback mechanisms.

This study aimed to investigate the presence of two vasomodulatory receptors, Piezo-1 and GPR4, on both the internal and external endothelial surfaces of the cavernous segment of the ICA, and to compare these findings with the cervical segment. ICA specimens from 10 human cadavers were dissected, processed through standard histological protocols, sectioned at 4 µm, and immunofluorescently stained. Receptor localization was evaluated using laser-scanning confocal microscopy.

GPR4 expression was detected exclusively on the external endothelial surface of the cavernous segment, specifically along the portion of the artery directly exposed to venous blood within the cavernous sinus. No Piezo-1 immunoreactivity was identified in this region. The luminal surfaces showed no expression of either receptor. Likewise, the cervical segment exhibited complete negativity for GPR4 and Piezo-1 throughout all histological layers.

Collectively, these findings indicate that the cavernous segment of the ICA exhibits a regionally specialized, pH-sensitive receptor profile mediated by GPR4. The absence of both receptors in the cervical segment supports the interpretation that this distribution is unique to the cavernous portion. The study suggests a potential biochemical feedback interface between venous return and arterial inflow in this anatomically distinct region and underscores the need for further functional and molecular investigations.