Inhibitory transmission in tenia coli mediated by distinct vasoactive intestinal peptide and apamin-sensitive pituitary adenylate cyclase activating peptide receptors.
Inhibitory transmission in tenia coli involves both vasoactive intestinal peptide (VIP) and an apamin-sensitive transmitter. The present study examined whether pituitary adenylate cyclase activating peptide (PACAP) is released from tenia coli and accounts for the apamin-sensitive component of neurally mediated relaxation. Electrical field stimulation (0.25-4 Hz) elicited frequency-dependent relaxation and PACAP release; earlier studies had shown a similar pattern for VIP release and an absence of nitric oxide generation in this tissue. A combination of specific PACAP-27 and PACAP-38 monoclonal antibodies (each 100 micrograms/ml), the PACAP antagonist PACAP6-38 and desensitization with PACAP inhibited relaxation induced by all frequencies of stimulation. The magnitude of inhibition elicited by each treatment (38 +/- 3%-41 +/- 3% at 4 Hz) was similar to that elicited by apamin (44 +/- 11%) and was not augmented by apamin. VIP antibody (1:60), the VIP antagonist, VIP10-28 and VIP desensitization also inhibited relaxation (33 +/- 2%-35 +/- 5% at 4 Hz). Inhibition by each treatment was augmented additively by apamin (76 +/- 3%-85 +/- 3%) as well as by combination with PACAP antibody, PACAP antagonist and PACAP desensitization (76 +/- 6%-80 +/- 3%). Measurements in muscle strips and dispersed tenia coil muscle cells showed that VIP10-28 inhibited relaxation induced by VIP only, and PACAP6-38 inhibited relaxation mediated by PACAP-27 or PACAP-38 only, implying interaction of VIP and PACAP with distinct receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Jin
J G
JG
Department of Physiology, Medical College of Virginia, Richmond.
Katsoulis
S
S
Schmidt
W E
WE
Grider
J R
JR
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002432:Cecum / Q000294:innervation / Q000378:metabolism*; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009433:Neural Inhibition; D009479:Neuropeptides / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000187:drug effects / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism*
D009479:Neuropeptides; 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