Upregulation of pituitary adenylate cyclase activating polypeptide and its receptor expression in the rat carotid body in chronic and intermittent hypoxia.

The carotid body (CB) plays important roles in cardiorespiratory changes in chronic and intermittent hypoxia. Pituitary adenylate cyclase activating polypeptide (PACAP) is involved in the regulation of respiratory chemoresponse. We hypothesized an upregulation of the expressions of PACAP and its receptor (PAC1) in the rat CB in chronic and intermittent hypoxia. The CB expressions of PACAP and PAC1 were examined in rats breathing 10% O(2) (in isobaric chamber for chronic hypoxia, 24 h/day) or in intermittent hypoxia (cyclic between air and 5% O(2) per minute, 8 h/day) for 7 days. Immunohistochemical studies showed that the PACAP and PAC1 proteins were localized in CB glomic clusters containing tyrosine hydroxylase. The proportional amount of cells with positive staining of PACAP and PAC1 was significantly increased in both hypoxic groups when compared with the normoxic control. In addition, the mRNA level of PAC1 expression was markedly elevated in the hypoxic groups, despite no changes in the PACAP expression. These results suggest an upregulation of PACAP and its receptor expression in the rat CB under chronic and intermittent hypoxic conditions. The PACAP binding to its receptor could activate the PKA signaling pathway leading to an increased CB excitability under hypoxic conditions.