Characterization of intestinal receptors for VIP and PACAP in rat and in PAC1 receptor knockout mouse.
The receptors for VIP and PACAP were characterized in vitro on rat ileal and colonic longitudinal smooth muscle with adherent myenteric ganglia. Colon strips from PAC1 receptor knockout and wildtype mice were also examined. VIP, PACAP-38 and PACAP-27 all caused concentration dependent relaxations. In rat ileum three different types of smooth muscle VIP/PACAP receptors were defined: (1) a PACAP-27 preferring receptor coupled to apamin sensitive Ca(2+)-dependent K+ channels, (2) a PAC1 receptor activated by both PACAP-27 and PACAP-38, and (3) a VIP specific receptor regulated by NPY. The receptors identified in rat colon were: (1) a PAC1 receptor localized on NO synthesizing neurones. Activation leads to increased NO production. (2) A smooth muscle PAC1 receptor. The responses elicited by both receptors were abolished by apamin. (3) A smooth muscle VIP specific receptor. PAC1 receptor knockout mice did not respond to PACAP-27 or PACAP-38, whereas VIP induced a relaxatory response indicating the presence of a VIP specific receptor. In wildtype mice all three peptides elicited relaxatory responses. Pharmacological characterization of intestinal VIP/PACAP receptors indicates the existence of receptors, such as a PACAP-27 preferring receptor and a VIP specific receptor, distinct from those that have been cloned (VPAC1, VPAC2, and PAC1).
Ekblad
E
E
Department of Physiological Sciences, Lund University, Lund, Sweden. eva.ekblad@mphy.lu.se
Jongsma
H
H
Brabet
P
P
Bockaert
J
J
Sundler
F
F
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D005260:Female; D007082:Ileum / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009126:Muscle Relaxation / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000235:genetics* / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
C495402:Adcyap1 protein, mouse; C495403:Adcyap1 protein, rat; C495504:Adcyap1r1 protein, mouse; C495505:Adcyap1r1 protein, rat; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; 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; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; C495507:Vipr1 protein, mouse; C495508:Vipr1 protein, rat; C495510:Vipr2 protein, mouse; C495511:Vipr2 protein, rat; D014660:Vasoactive Intestinal Peptide