# Desensitization of beta1 adrenergic receptor-nitric oxide signaling in cardiac diseases

> **NIH VA I01** · VA NORTHERN CALIFORNIA HEALTH CARE SYS · 2021 · —

## Abstract

Emerging evidence indicates that nitric oxide (NO) is involved in cardiac β1 adrenergic receptor
(β1AR) stimulation of cardiac function. We propose that scaffold protein SAP97 plays a critical
role in regulation of cardiac β1AR-induced NOS1-NO signaling cascade via organizing a β1AR-
NOS1 signalosome. This pathway is necessary for regulation of cardiac contractile function. We
also hypothesize that G-protein kinase 5 (GRK5) promotes phosphorylation of cardiac β1AR
PDZ motif and dissociation of the receptor from the SAP97-organized signalosome for activation
of NOS1-NO signaling and promotes desensitization of receptor signaling in cardiac diseases.
We will test the hypotheses with the following aims. Aim 1. SAP97 regulates β1AR-induced NO
signaling in heart. Aim 2. SAP97 maintains the integrity of β1AR-SAP97-NOS1 signalosome to
preserve cardiac function. Aim 3. GRK5 promotes desensitization of β1AR-NO signaling via
disruption of the receptor-SAP97 signalosome in heart failure.

## Key facts

- **NIH application ID:** 10121283
- **Project number:** 1I01BX005100-01A1
- **Recipient organization:** VA NORTHERN CALIFORNIA HEALTH CARE SYS
- **Principal Investigator:** YANG Kevin XIANG
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10121283

## Citation

> US National Institutes of Health, RePORTER application 10121283, Desensitization of beta1 adrenergic receptor-nitric oxide signaling in cardiac diseases (1I01BX005100-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10121283. Licensed CC0.

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