P. Hedlund et al., PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE, HELOSPECTIN, AND VASOACTIVE INTESTINAL POLYPEPTIDE IN HUMAN CORPUS CAVERNOSUM, British Journal of Pharmacology, 116(4), 1995, pp. 2258-2266
1 The distribution and effects of pituitary adenylate cyclase-activati
ng polypeptide (PACAP-27 and -38), helospectin (Hel-1 and Hel-2), and
vasoactive intestinal polypeptide (VIP), were investigated in isolated
preparations of human corpus cavernosum (CC). 2 Immunohistochemistry
revealed coinciding profiles of nerve structures that showed immunorea
ctivities for VIP and PACAP, and VIP and Hel. Confocal microscopy show
ed the co-existence of VIP- and PACAP-immunoreactivities, and VIP- and
Hel-immunoreactivities in most (90%) varicose nerve structures. 3 As
determined by radioimmunoassay, the amounts of VIP, PACAP-27, and PACA
P-38 in the preparations were 61.7 +/- 11.6, 0.1 +/- 0.05, and 3.7 +/-
0.5 pmol g(-1) wet weight of tissue (pmol g(-1) wet wt), respectively
. In tissue from patients with diabetes, the content of VIP was lower
(13.7 +/- 0.5 pmol g(-1) wet wet wt), whereas that of PACAP (-27 and -
38) was unchanged. 4 Cyclic nucleotide levels were determined in prepa
rations exposed to PACAP-27, PACAP-38, Hel-l, Hel-2, and VIP. Ah the p
eptides, but Hel-2, significantly increased the concentrations of cycl
ic AMP, whereas the levels of cyclic GMP were unchanged. 5 The peptide
s concentration-dependently relaxed noradrenaline-contracted preparati
ons. The order of potency was VIP > PACAP 27 > Hel-1 > Hel-2 > PACAP-3
8. 6 Hel-1, VIP and PACAP-27 effectively counteracted electrically ind
uced contractions. At 10(-6) M, the highest peptide concentration used
, the inhibitory effects obtained reached 96 +/- 3%, 87 +/- 6%, and 80
+/- 3%, respectively. 7 The results suggest that PACAP and Hel-1 are
co-localized with VIP in nerve structures within the human cavernous t
issue, and that the peptides are effective relaxants of CC preparation
s ipl vitro. The role of the investigated peptides for penile erection
remains to be established.