Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0020440 (
hypercapnia
)
7,939
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The evidence is mounting for a role for abnormal signaling of the stress peptide, pituitary adenylate cyclase activating polypeptide (PACAP), and its canonical receptor,
PAC1
, in the pathogenesis of sudden infant death syndrome (SIDS). In this study, we investigated whether the PACAP receptors,
PAC1
or VPAC2, are involved in the neonatal cardiorespiratory response to hypercapnic stress. We used head-out plethysmography and surface ECG electrodes to assess cardiorespiratory responses to an 8% hypercapnic challenge in unanesthetized and spontaneously breathing 4 days old
PAC1
or VPAC2 knockout (KO) and wildtype (WT) mouse pups. We demonstrate that compared to WTs, breathing frequency (RR) and minute ventilation () in
PAC1
KO pups were significantly blunted in response to
hypercapnia
. Although heart rate was unaltered in
PAC1
KO pups during
hypercapnia
, heart rate recovery post-
hypercapnia
was impaired. In contrast, cardiorespiratory impairments in VPAC2 KO pups were limited to only an overall higher tidal volume (V
T
), independent of treatment. These findings suggest that PACAP signaling through the
PAC1
receptor plays a more important role than signaling through the VPAC2 receptor, in neonatal respiratory responses to
hypercapnia
. Thus, deficits in PACAP signaling primarily via
PAC1
may contribute to the inability of infants to mount an appropriate protective response to homeostatic stressors in childhood disorders such as SIDS.
...
PMID:Impaired cardiorespiratory responses to hypercapnia in neonatal mice lacking PAC1 but not VPAC2 receptors. 3314 56
