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

The concentration of pituitary adenylyl cyclase-activating polypeptide [PAC AP-(1-38)] in porcine adrenal glands amounted to 14 +/- 3 pmol/g tissue. PA CAP immunoreactive (PACAP-IR) fibers innervated adrenal chromaffin cells (o ften co-localized with choline acetyltransferase). Subcapsular fibers trave rsed the cortex-innervating endocrine cells and blood vessels [some co-stor ing mainly calcitonin gene-related peptide but also vasoactive intestinal p olypeptide (VIP)]. PACAP-IR fibers were demonstrated in the splanchnic nerv es, whereas IR adrenal nerve cell bodies were absent. In isolated, vascular ly perfused adrenal gland, splanchnic nerve stimulation (16 Hz) and capsaic in (10(-5) M) increased PACAP-(1-38) release (1.6-fold and 6-fold respectiv ely, P = 0.02). PACAP-(1-38) dose-dependently stimulated cortisol (2 x 10(- 10) M; 24-fold increase, P = 0.02) and chromogranin A fragment (2 x 10(-9) M; 15-fold increase, P = 0.05) secretion. Both were strongly inhibited by t he PAC(1)/VPAC(2) receptor antagonist PACAP-(6-38) (10(-7) M). PACAP-(6-38) also inhibited splanchnic nerve (10 Hz)-induced cortisol secretion but lac ked any effect on splanchnic nerve-induced pancreastatin secretion. PACAP-( 1-38) (2 x 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 c onclude that PACAP-(1-38) may play a role in splanchnic nerve-induced adren al secretion and in afferent reflex pathways.