What is the mechanism of action of Vasoactive Intestinal Peptide (VIP)?

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Mechanism of Action of Vasoactive Intestinal Peptide (VIP)

Vasoactive intestinal peptide (VIP) primarily induces splanchnic vasodilation, inhibits gastric acid secretion, and regulates gastrointestinal motility through its interaction with specific membrane receptors that activate the cyclic AMP pathway. 1

Primary Mechanisms of VIP Action

Vascular Effects

  • VIP functions as a potent vasodilator, particularly in the splanchnic circulation
  • Induces splanchnic vasodilation that can result in hypotension and systemic hemoconcentration 1
  • This vasodilatory effect contributes to its role in early dumping syndrome following gastric surgery

Gastrointestinal Effects

  • Inhibition of gastric acid secretion:

    • VIP predominantly inhibits gastric acid secretion through stimulation of somatostatin release 2
    • The inhibitory effect on acid secretion is sustained due to somatostatin's influence
    • This contradicts earlier research suggesting VIP stimulates gastric acid secretion 3

  • Regulation of GI motility:

    • Affects gastrointestinal smooth muscle function
    • Contributes to discoordinated GI motility when released in excess 1

Cellular Signaling Pathway

  • Binds to specific VIP receptors on cell membranes (primarily 64 kDa glycoproteins) 4
  • Receptor activation triggers a large increase in intracellular cyclic AMP levels 4
  • After binding, VIP undergoes receptor-mediated endocytosis, followed by:
    • Degradation of VIP in lysosomes
    • Recycling of most receptors back to the cell surface 4

Physiological and Pathological Roles

Normal Physiological Functions

  • Regulates ion secretion in the gut
  • Influences nutrient absorption
  • Controls gut motility
  • Contributes to glycemic control
  • Plays a role in circadian rhythm regulation 5

Role in Pathological Conditions

  • Dumping Syndrome:

    • Increased release of VIP contributes to early dumping syndrome after gastric surgery 1
    • Along with neurotensin, VIP mediates vasodilation and hemodynamic effects seen in early dumping
    • These effects include tachycardia, hypotension, and systemic hemoconcentration 1

  • Pulmonary Hypertension:

    • VIP levels are decreased in pulmonary arterial hypertension (PAH) patients
    • Exogenous VIP may decrease pulmonary artery pressure and pulmonary vascular resistance
    • VIP inhibits platelet activation and reduces pulmonary artery smooth muscle cell proliferation 1

Clinical Implications

  • VIP's inhibitory effect on gastric acid secretion makes it a potential therapeutic target for acid-related disorders
  • Its vasodilatory properties and effects on smooth muscle function explain its role in dumping syndrome
  • Decreased VIP levels in PAH suggest potential therapeutic applications for VIP analogs in this condition 1
  • VIP's broad physiological effects make it relevant to diabetes, autoimmune diseases, and cancer research 5

Important Considerations

  • VIP's effects can vary depending on concentration, target tissue, and physiological context
  • The peptide belongs to a family of cerebrogastrointestinal oligopeptides with multiple functions
  • VIP's action on acid secretion involves complex interactions with other regulatory peptides, particularly somatostatin 2
  • The inhibitory effect of VIP on acid secretion appears more prominent than any stimulatory effects in physiological conditions

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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