Two receptors for vasoactive intestinal polypeptide with similar specificity and complementary distributions

Area of Science:

• Neuroscience
• Endocrinology
• Molecular Biology

Background:

• Vasoactive intestinal polypeptide (VIP) is a peptide with diverse physiological roles.
• Pharmacological studies suggested VIP acts via multiple receptors.
• The cloning of two distinct VIP receptors, VIP1 and VIP2, confirmed this hypothesis.

Purpose of the Study:

• To characterize the distinct properties and tissue distribution of the cloned VIP1 and VIP2 receptors.
• To understand the differential signaling pathways and physiological implications of VIP receptor subtypes.

Main Methods:

• Receptor cloning and sequencing to determine amino acid differences.
• In situ hybridization histochemistry to map the distribution of VIP1 and VIP2 receptor messenger RNAs (mRNAs).
• Assays to determine the potency of VIP, PHI, PACAP38, and PACAP27 on both receptor types.

Main Results:

• VIP1 and VIP2 receptors exhibit very different amino acid sequences.
• VIP, PHI, PACAP38, and PACAP27 show similar potency at both VIP1 and VIP2 receptors.
• Secretin uniquely activates the VIP1 receptor.
• VIP1 receptor mRNA is found in the lung, small intestine, thymus, cerebral cortex, and hippocampus.
• VIP2 receptor mRNA is detected in the stomach, testes, neuroendocrine hypothalamus, pituitary, and pancreatic islets, with distinct distribution from VIP1.

Conclusions:

• The distinct sequences and differential mRNA distributions of VIP1 and VIP2 receptors indicate specialized functions.
• VIP1 and VIP2 receptors mediate distinct physiological processes in the central nervous system and peripheral tissues.
• Understanding these receptor subtypes is crucial for elucidating VIP's role in neuroendocrine and other functions.