Gj. Geng et al., ROLE OF L-TYPE CA2-INDUCED ADRENAL CATECHOLAMINE RELEASE IN-VIVO( CHANNEL IN PACAP), American journal of physiology. Regulatory, integrative and comparative physiology, 42(4), 1997, pp. 1339-1345
The aim of the present study was to investigate whether the dihydropyr
idine-sensitive L-type Ca2+ channel is operative in adrenal catecholam
ine (CA) secretion induced by a novel neuropeptide, pituitary adenylat
e cyclase-activating polypeptide (PACAP), in anesthetized dogs. Plasma
CA concentrations in adrenal venous and aortic blood were determined
by a high-performance liquid chromatography method. All drugs tested w
ere locally infused into the left adrenal gland via the left adrenolum
bar artery. PACAP, with the isoform consisting of 27 (PACAP-27) and 38
(PACAP-38) amino acid residues, significantly increased CA output in
a dose-dependent manner, with doses ranging from 5 to 500 ng and 7 to
700 ng, respectively. However, the amplitude of epinephrine response t
o PACAP-27 was three times greater than that obtained with PACAP-38 at
the highest dose tested. In a separate group, a single dose of PACAP-
27 (50 ng) induced highly reproducible CA responses when the same dose
was repeated with an interval of 35 min. In dogs treated with nifedip
ine (50 mu g), 5 min before the second administration of PACAP-27, the
net CA response was significantly inhibited by similar to 50% compare
d with that obtained in the presence of vehicle. A similar CA response
to BAY K 8644 (5 mu g) was completely abolished by the same dose of n
ifedipine. The present results indicate that both PACAP-27 and PACAP-3
8 have the direct local secretagogue effect on the adrenal medulla in
vivo and that CA responses to PACAP-27 were greater than those observe
d with PACAP-38 at equivalent mole doses. The study suggests that the
dihydropyridine-sensitive L-type Ca2+ channel is functionally involved
in PACAP-induced adrenal CA secretion in the canine adrenal medulla i
n vivo.