Stress peptide PACAP stimulates and stabilizes neonatal breathing through distinct mechanisms

• Mice deficient in stress peptide PACAP have a SIDS-like phenotype.
• We examined effects of PACAP on neonatal breathing in rats using the neonatal working heart brainstem preparation.
• We found that exogenous PACAP stimulates and stabilizes neonatal breathing.
• The stimulatory effect of PACAP required intact carotid bodies; the stabilizing effect persisted after carotid body denervation.

Pituitary adenylate cyclase-activating peptide (PACAP) is an important mediator of the stress response and is crucial in maintaining breathing in neonates. Here we investigate the role of exogenously applied PACAP in neonatal breathing using the neonatal rat in situ working heart-brainstem preparation. A 1-min bolus of 250 nM PACAP-38 caused an increased in respiratory frequency that was rapid and transient, but had no effect on neural tidal volume or neural minute ventilation. Denervation of the carotid body abolished this effect. PACAP had a persistent effect on breathing stability in both carotid body-intact and -denervated preparations, as shown by decreases in respiratory variability 5 min following application. These data suggest that PACAP released during stress acts via carotid body dependent and independent mechanisms to stimulate and stabilize breathing. These mechanisms may account for PACAP's critical role in defending neonatal breathing against environmental stress.