Description

Product Description

Ro 25-1553 is a synthetic 31-amino-acid peptide analog of vasoactive intestinal peptide (VIP), specifically engineered to act as a highly selective VPAC2 receptor agonist. It mimics the natural neuropeptide VIP while improving receptor selectivity, metabolic stability, and pharmacological potency.

VIP, a member of the secretin/glucagon family of neuropeptides, is distributed widely throughout the central and peripheral nervous systems, lungs, and gastrointestinal tract. It exerts diverse biological actions including vasodilation, bronchodilation, smooth muscle relaxation, and modulation of immune responses. However, native VIP is rapidly degraded by peptidases, limiting its research and therapeutic utility.

Ro 25-1553 was developed to overcome these limitations by incorporating structural modifications that confer resistance to enzymatic degradation and enhance selectivity for the VPAC2 receptor subtype (also known as VIP2 receptor). This analog provides researchers with a reliable and longer-acting tool for exploring respiratory physiology, neuropeptide pharmacology, and pulmonary disorders such as asthma and chronic obstructive pulmonary disease (COPD).

Key Features

• Selective VPAC2 receptor agonist with reduced VPAC1 affinity

• Enhanced metabolic stability compared to native VIP

• Potent bronchodilator and smooth muscle relaxant

• Non-tachyphylactic action with prolonged activity

• Useful for studies in airway physiology, pulmonary pharmacology, and neuroimmunology

Research Background

VIP and its receptors (VPAC1 and VPAC2) are G protein–coupled receptors (GPCRs) involved in smooth muscle tone regulation, glandular secretion, and vasodilation. VPAC2 receptors are primarily expressed in the respiratory tract, pancreas, immune cells, and central nervous system. Selective activation of VPAC2 leads to bronchodilation without triggering major cardiovascular effects, making Ro 25-1553 a valuable pharmacological probe.

Preclinical studies show that Ro 25-1553 induces dose-dependent relaxation of airway smooth muscle in guinea pig models exposed to carbachol or electrical field stimulation. It demonstrates prolonged bronchodilation due to resistance against degradation by neutral endopeptidases and dipeptidyl peptidase IV (DPP-IV).

Product Specifications

Mechanism of Action

1. VPAC2 Receptor Selectivity

Ro 25-1553 is a highly selective agonist for the VPAC2 receptor, a subtype of the vasoactive intestinal peptide receptors (VPAC1 and VPAC2). Both receptors are coupled to Gs proteins that stimulate adenylyl cyclase and elevate intracellular cAMP levels. However, VPAC2 activation primarily mediates bronchodilation, vasodilation, and smooth muscle relaxation, while VPAC1 is more involved in gastrointestinal secretion and vasomotor control.

By favoring VPAC2 over VPAC1, Ro 25-1553 minimizes unwanted side effects such as gastrointestinal motility changes or hypotension, thereby offering cleaner pharmacological specificity.

2. Airway Smooth Muscle Relaxation

Ro 25-1553 binds to VPAC2 receptors on airway smooth muscle cells, stimulating adenylyl cyclase and increasing cAMP levels. The elevated cAMP activates protein kinase A (PKA), leading to:

• Inhibition of myosin light-chain kinase (MLCK) activity

• Reduction in intracellular Ca²⁺ levels

• Relaxation of contracted tracheal smooth muscle fibers

This sequence of intracellular events culminates in potent and sustained bronchodilation, which can reverse constriction induced by cholinergic agents such as carbachol or acetylcholine.

3. Neural and Immune Modulation

VPAC2 receptors are also expressed in immune and neural tissues. Ro 25-1553 has been shown to:

• Suppress pro-inflammatory cytokine release from macrophages and T-cells

• Modulate cholinergic nerve transmission in airway regulation

• Protect against oxidative and inflammatory stress in pulmonary models

These actions highlight its potential role not only as a bronchodilator but also as a neuroimmune modulator that contributes to the maintenance of airway homeostasis.

4. Signaling Pathways

The main downstream effects of VPAC2 activation by Ro 25-1553 include:

• cAMP accumulation → PKA activation → smooth muscle relaxation

• Phosphorylation of CREB → gene regulation for cytoprotection

• Inhibition of NF-κB → reduced inflammatory cytokine transcription

• NO synthesis enhancement → vascular and airway smooth muscle relaxation

Collectively, these mechanisms make Ro 25-1553 an indispensable research tool for dissecting the roles of VPAC2 in pulmonary and vascular systems.

Side Effects

As a VIP analog, Ro 25-1553 shares several pharmacodynamic properties with its natural counterpart, but its selectivity for VPAC2 minimizes side effects associated with VPAC1 or PAC1 activation. In preclinical settings, the following have been observed:

• Mild hypotension at high concentrations due to vasodilation

• Transient flushing or vascular relaxation effects

• Minor gastrointestinal motility changes (less pronounced than native VIP)

• Receptor desensitization with prolonged high-dose exposure

• Reduced inflammation through immunomodulation, typically beneficial

No significant toxicity or mutagenicity has been reported in controlled laboratory models. The compound is stable and safe under recommended experimental conditions but is not intended for therapeutic or diagnostic use in humans.

Disclaimer

For research use only. Not for human or veterinary use, diagnosis, or treatment.

Keywords

Ro 25-1553, VPAC2 receptor agonist, VIP analog, bronchodilator, vasoactive intestinal peptide mimetic, airway smooth muscle relaxation, pulmonary pharmacology, GPCR ligand, cAMP signaling, neuropeptide research.

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