The evaluation of
peptide receptors in man is needed not only to discover the physiological target tissues of a given
peptide but also to identify diseases with a sufficient receptor overexpression for diagnostic or therapeutic interventions.
Vasoactive intestinal peptide (VIP) and pituitary
adenylate cyclase-activating
peptide (
PACAP) receptors have been evaluated in human
tumors and in their tissues of origin using in vitro receptor autoradiography with 125I-VIP or 125I-acetyl-PACAP-27 in tissue sections. The VIP/
PACAP receptor subtypes VPAC1, VPAC2, and PAC1 were evaluated in these tissues by determining the rank order of potencies of VIP and
PACAP as well as VPAC1- and VPAC2-selective analogues. The VIP/
PACAP receptors expressed in the great majority of the most frequently occurring human
tumors, including breast (100% receptor incidence), prostate (100%), pancreas (65%), lung (58%), colon (96%), stomach (54%), liver (49%), and urinary bladder (100%)
carcinomas as well as
lymphomas (58%) and
meningiomas (100%), are predominantly of the VPAC1 type. Their cells or tissues of origin, i.e., hepatocytes, breast lobules and ducts, urothelium, prostate glands, pancreatic ducts, lung acini, gastrointestinal mucosa, and lymphocytes, also predominantly express VPAC1.
Leiomyomas predominantly express VPAC2 receptors, whereas
paragangliomas,
pheochromocytomas, and
endometrial carcinomas preferentially express PAC1 receptors. Conversely, VPAC2 receptors are found mainly in smooth muscle (i.e., stomach), in vessels, and in stroma (e.g., of the prostate), whereas PAC1 receptors are present in the adrenal medulla and in some uterine glands. Whereas the very wide distribution of VIP/
PACAP receptors in the normal human body is indicative of a key role of these
peptides in human physiology, the high VIP/
PACAP receptor expression in
tumors may represent the molecular basis for clinical applications of VIP/
PACAP such as in vivo scintigraphy and
radiotherapy of
tumors as well as VIP/
PACAP analogue treatment for
tumor growth inhibition.