The evaluation of peptide receptors in man is relevant to identifying the physiological target tissues of a given peptide and to selecting diseases with a sufficient receptor overexpression for diagnostic or therapeutic intervention. VIP/PACAP receptors have been evaluated in normal and diseased human non-neuronal tissues by using in vitro receptor autoradiography with 125I-VIP or 125I-PACAP in tissue sections. As assessed by subtype-selective VIP analogs, VIP receptors of the VPAC1 subtype are found in a wide variety of tissues including liver, breast, kidney, prostate, ureter, bladder, pancreatic ducts, gastrointestinal mucosa, lung, thyroid, adipose, and lymphoid tissues. VPAC2 receptors are predominantly found in vessels and smooth muscles, whereas PAC1 receptors are present in the adrenal medulla. VIP/PACAP receptors are expressed in the majority of the most frequently occurring human tumors, including breast, prostate, pancreas, lung, colon, stomach, liver, and bladder carcinomas, as well as lymphomas and meningiomas, predominantly as VPAC1 receptors, as do their tissues of origin. Although leiomyomas predominantly express VPAC2 receptors, glial tumors, pituitary adenomas, neuroblastomas, paragangliomas, pheochromocytomas, and endometrial carcinomas preferentially express PAC1 receptors. The very wide distribution of VIP/PACAP receptors in the normal human body is indicative of the key role of these peptides in human physiology and pathophysiology. Moreover, the receptor expression in tumors is the molecular basis for clinical applications of VIP/PACAP such as in vivo scintigraphy and radiotherapy of tumors as well as VIP/PACAP analog treatment for tumor growth inhibition.
