PACAP-(1–38) as neurotransmitter in the porcine adrenal glands

Abstract

The concentration of pituitary adenylyl cyclase-activating polypeptide [PACAP-(1–38)] in porcine adrenal glands amounted to 14 ± 3 pmol/g tissue. PACAP immunoreactive (PACAP-IR) fibers innervated adrenal chromaffin cells (often co-localized with choline acetyltransferase). Subcapsular fibers traversed the cortex-innervating endocrine cells and blood vessels [some co-storing mainly calcitonin gene-related peptide but also vasoactive intestinal polypeptide (VIP)]. PACAP-IR fibers were demonstrated in the splanchnic nerves, whereas IR adrenal nerve cell bodies were absent. In isolated, vascularly perfused adrenal gland, splanchnic nerve stimulation (16 Hz) and capsaicin (10−5 M) increased PACAP-(1–38) release (1.6-fold and 6-fold respectively, P = 0.02). PACAP-(1–38) dose-dependently stimulated cortisol (2 × 10−10 M; 24-fold increase, P = 0.02) and chromogranin A fragment (2 × 10−9 M; 15-fold increase, P = 0.05) secretion. Both were strongly inhibited by the PAC1/VPAC2 receptor antagonist PACAP-(6–38) (10−7 M). PACAP-(6–38) also inhibited splanchnic nerve (10 Hz)-induced cortisol secretion but lacked any effect on splanchnic nerve-induced pancreastatin secretion. PACAP-(1–38) (2 × 10−10 M) decreased vascular resistance from 5.5 ± 0.6 to 4.6 ± 0.4 mmHg · min · ml−1. PACAP-(6–38) had no effect on this response. We conclude that PACAP-(1–38) may play a role in splanchnic nerve-induced adrenal secretion and in afferent reflex pathways.