Distinct receptors mediate pituitary adenylate cyclase-activating peptide- and vasoactive intestinal peptide-induced relaxation of rat ileal longitudinal muscle.
Relaxant responses to pituitary adenylate cyclase-activating peptide (PACAP)-27, PACAP-38 and vasoactive intestinal peptide (VIP) were examined in rat ileal longitudinal muscle. PACAP-27 was much more potent than PACAP-38 and VIP, with PACAP-38 and VIP being equipotent. The relaxation induced by each of the peptides was unaffected by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) (10[-4] M), tetrodotoxin (10[-6] M) or atropine (10[-6] M). Pretreatment with apamin (10[-6] M) abolished the relaxations induced by PACAP-27, but not those induced by PACAP-38 or VIP. Pretreatment with neuropeptide Y (NPY) (10[-7] M) inhibited relaxations induced by VIP, but not those induced by PACAP-27 or PACAP-38. No cross-desensitization between PACAP-27 and VIP could be revealed. In conclusion, distinct receptors mediate PACAP- and VIP-induced relaxations of rat ileal longitudinal muscle. At least three different types of receptors may exist: (1) a PACAP-27 preferring receptor coupled to apamin sensitive Ca2+-dependent K+ channels, (2) a PACAP specific receptor activated by both PACAP-27 and PACAP-38 but not by VIP and (3) a VIP specific receptor regulated by NPY by yet unknown mechanisms.
Ekblad
E
E
Department of Physiology and Neuroscience, University of Lund, University Hospital, Experimental Research Center, Sweden. eva.ekblad@mphy.lu.se
Sundler
F
F
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007082:Ileum / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009478:Neuropeptide Y / Q000494:pharmacology; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000187:drug effects* / Q000502:physiology; D018005:Receptors, Vasoactive Intestinal Peptide / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*
C495403:Adcyap1 protein, rat; D004791:Enzyme Inhibitors; D009478:Neuropeptide Y; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D001030:Apamin; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester