Abstract
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G-protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [1]. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family.
The secretin-like GPCRs include secretin [2], calcitonin [3], parathyroid hormone/parathyroid hormone-related peptides [4] and vasoactive intestinal peptide [5], all of which activate adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. The amino acid sequences of the receptors contain high proportions of hydrophobic residues grouped into 7 domains, in a manner reminiscent of the rhodopsins and other receptors believed to interact with G-proteins. However, while a similar 3D framework has been proposed to account for this, there is no significant sequence identity between these families: the secretin-like receptors thus bear their own unique '7TM' signature.
Vasoactive intestinal polypeptide (VIP) has a wide physiological profile.
In the periphery, it induces relaxation in smooth muscle; inhibits
secretion in certain tissues, but stimulates secretion in others; and
modulates activity of cells in the immune system [6]. In the CNS, it has a
range of both excitatory and inhibitory actions. VIP receptors are
distributed widely in the periphery, and occur throughout the gastrointestinal tract and genitourinary system, other smooth muscles and
secretory glands. In the CNS, they are found abundantly in, e.g. the cortex,
hippocampus and thalamus [6]. All VIP receptors activate adenylyl cyclase. |