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, respectively. One class of PACAP receptors was defined from (125)I-labeled PACAP-27 binding experiments (dissociation constant = 5.2 nM; maximum binding capacity = 5.2 pmol/mg protein) with a specificity: PACAP-27 approximately VIP > helodermin approximately peptide histidine-methionine (PHM) >> secretin. Two classes of VIP receptors were established with (125)I-VIP (dissociation constants of 5.4 and 197 nM) with a specificity: VIP approximately helodermin approximately PACAP-27 >> PHM >> secretin. PACAP-27 and VIP were equipotent on adenylyl cyclase stimulation (EC(50) = 1.6 nM), whereas other peptides showed lower potency (helodermin > PHM >> secretin). PACAP/VIP antagonists supported that PACAP-27 acts in the human lung through either specific receptors or common PACAP/VIP receptors. The present results are the first demonstration of the presence of PAC(1) receptors and extend our knowledge of common PACAP/VIP receptors in the human lung.
Department of Biochemistry and Molecular Biology, University of Alcalá, 28871 Alcalá de Henares, Spain.
R
R
Busto
I
I
Carrero
L G
LG
Guijarro
R M
RM
Solano
J
J
Zapatero
F
F
Noguerales
J C
JC
Prieto
D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D006801:Humans; D007124:Immunoenzyme Techniques; D008168:Lung / Q000378:metabolism*; D008875:Middle Aged; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018005:Receptors, Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism
C495401:ADCYAP1 protein, human; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D020033:Protein Isoforms; D012333:RNA, Messenger; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D000262:Adenylyl Cyclases