Action of pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal polypeptide on the rat vascular system: effects on blood pressure and receptor binding.
The N-terminal fragment (PACAP 27) of the novel neuropeptide, pituitary adenylate cyclase-activating polypeptide 38 (PACAP 38), has 68% homology with vasoactive intestinal polypeptide (VIP). The administration of bolus doses of PACAP 38 and its 27 amino acid N-terminal fragment (PACAP 27) caused a rapid but transient dose-dependent hypotensive effect in the anaesthetized rat. The amplitude and duration of the response obtained by PACAP 38 was comparable with VIP whereas PACAP 27 was three times less potent than VIP. Furthermore, radioreceptor binding studies demonstrated that 125I-labelled PACAP 27 and 125I-labelled VIP bound to membranes prepared from blood vessels. Both PACAP 27 and VIP were capable of displacing the other from these binding sites. We propose that the hypotensive effect is via the same receptor type.
Nandha
K A
KA
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London.
Benito-Orfila
M A
MA
Smith
D M
DM
Ghatei
M A
MA
Bloom
S R
SR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000378:metabolism; D002319:Cardiovascular System / Q000187:drug effects*; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology*
C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide