Expression, pharmacological, and functional evidence for PACAP VIP receptors in human lung

Pituitary adenylate cyclase-activating peptide (PACAP) type 1 (PAC(1)) and common PACAP/vasoactive intestinal peptide (VIP) type 1 and 2 (VPAC(1) and VPAC(2), respectively) receptors were detected in the human lung by RT-PCR. The proteins were identified by immunoblotting at 72, 67, and 68 kDa, resp ectively. One class of PACAP receptors was defined from I-125-labeled PACAP -27 binding experiments (dissociation constant = 5.2 nM; maximum binding ca pacity = 5.2 pmol/mg protein) with a specificity: PACAP-27 approximate to V IP > helodermin approximate to peptide histidine-methionine (PHM) >> secret in. Two classes of VIP receptors were established with I-125-VIP (dissociat ion constants of 5.4 and 197 nM) with a specificity: VIP approximate to hel odermin approximate to PACAP-27 >> PHM >> secretin. PACAP-27 and VIP were e quipotent on adenylyl cyclase stimulation (EC50 = 1.6 nM), whereas other pe ptides showed lower potency (helodermin > PHM >> secretin). PACAP/VIP antag onists supported that PACAP-27 acts in the human lung through either specif ic receptors or common PACAP/VIP receptors. The present results are the fir st demonstration of the presence of PAC(1) receptors and extend our knowled ge of common PACAP/VIP receptors in the human lung.