Upregulation of Pituitary Adenylate Cyclase Activating Polypeptide and Its Receptor Expression in the Rat Carotid Body in Chronic and Intermittent Hypoxia

Abstract

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.

Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Signalling Exerts Chondrogenesis Promoting and Protecting Effects: Implication of Calcineurin as a Downstream Target

“…The applied oxidative stress regime decreased the protein expression of PKA, CREB, Sox9 and lowered the phosphorylation level of both transcription factors. The increased protein expression of PAC1 receptor is an interesting phenomenon; however, similar results were observed in rat carotid body under hypoxic conditions [69] or in global brain ischemia in mice [70]; it may be a general cellular response to allow an enhanced PACAP signalling in order to obtain a more efficient cellular protection.…”

Single cell transcriptome analysis of mouse carotid body glomus cells

“…; Lam et al . ), as well as two unreported GPCRs, latrophilin receptor (Lphn1) and Leucine‐rich repeat‐containing GPCR (Lgr5). The list of GPCRs with less abundant sequencing reads in our single cell RNA‐Seq (genes ranked blow the top 10%) also included previously identified CB GPCRs, such as type‐1A angiotensin II receptor (Agtr1a), dopamine receptor (Drd2) and endothelin‐1 receptor (Ednra) (Gauda et al .…”

“…PACAP and its receptor have also been shown to be present in rat CB (Lam et al . ). Interestingly, PACAP alone is sufficient to demonstrate stimulatory effects on CB glomus cells that could be attenuated upon PKA inhibition, further suggesting the importance of cAMP in CB chemosensory transduction (Lam et al .…”

“…Interestingly, PACAP alone is sufficient to demonstrate stimulatory effects on CB glomus cells that could be attenuated upon PKA inhibition, further suggesting the importance of cAMP in CB chemosensory transduction (Lam et al . ). Although an increase in cAMP is associated with increased glomus cell activation, the CB can also take advantage of the inhibitory autocrine regulation via G α i ‐coupled receptors (e.g.…”

Vasoactive Intestinal Polypeptide in the Carotid Body—A History of Forty Years of Research. A Mini Review

“…It is the second member of a glucagon/secretin superfamily which has been found in this organ. PACAP, which is characterized as having 68% sequence homology with VIP, has been noted in the type-I glomus cells, where specific G-protein coupled receptors for this peptide-PAC1-have also been found [95]. It should also be pointed out that PACAP, apart from PAC1, may interact with VPAC1 and VPAC2, whereby VPAC1 and VPAC2 bind VIP and PACAP with equal affinities.…”