FUNCTIONAL AND METABOLIC EVIDENCE FOR 2 DIFFERENT VANILLOID (VN1 AND VN2) RECEPTORS IN PERFUSED RAT HINDLIMB

Vanilloid spice principles, including capsaicin, stimulate vasoconstri ction in the rat hindlimb perfused at constant flow and, depending on dose, either stimulate or inhibit oxygen consumption by this vascular bed. We now present metabolic and functional evidence for two differen t vanilloid (VN1 and VN2) receptor types. These receptors can be disti nguished on the basis of their differing agonist affinity for capsaici n, their different calcium and oxygen dependencies for inducing vasoco nstriction, and whether they stimulate, or inhibit, oxygen consumption . The higher affinity vanilloid receptor, VN1 can be distinguished on the basis of initiating vasoconstriction at low doses of capsaicin and simultaneously stimulating oxygen consumption. Its apparent biologica l function is dependent on the presence of oxygen and external calcium . In contrast, the lower affinity receptor, VN2 induces vasoconstricti on associated with inhibition of oxygen consumption. Its vasoconstrict ion action can occur independently of either external calcium ions, or the presence of oxygen in the perfusate.