Similarities between the relaxations induced by vasoactive intestinal peptide and by stimulation of the non-adrenergic non-cholinergic neurons in the rat stomach.
The characteristics of the non-adrenergic, non-cholinergic inhibitory response of the rat stomach fundus to transmural nerve stimulation were compared with the relaxation induced by vasoactive intestinal polypeptide (VIP). Treatment with alpha-chymotrypsin (5 U/ml) or VIP antiserum (1:200) significantly reduced the relaxation induced by transmural nerve stimulation at 30 Hz, indicating that the possible transmitter in the non-adrenergic, non-cholinergic nerves is a peptide and may be VIP or a closely related peptide. VIP was able to relax, fully and dose-dependently, the stomach fundus that had previously been constricted by treatment with 10(-6) M serotonin, and the IC50 value for VIP was 2.4 X 10(-9) M. VIP elevated levels of cyclic AMP in a dose-dependent manner and the EC50 value was 2.8 X 10(-9) M in the presence of 10(-6) M atropine and 10(-6) M guanethidine. The stomach fundus was relaxed by transmural nerve stimulation (30 Hz, 50 mA) and transmural nerve stimulation also caused production of cyclic AMP in the rat stomach in the presence of atropine and guanethidine. The basal level of cyclic AMP in the stomach was 8.7 +/- 0.26 pmole/mg protein. When transmural nerve stimulation was applied for 5 min, the contraction of the stomach, induced by 10(-6) M serotonin, was inhibited by 54% in the presence of atropine and guanethidine and the level of cyclic AMP was increased to 13.0 +/- 0.73 pmol/mg protein. Apamin inhibited the transmural nerve stimulation-induced relaxation and shifted the dose-response curve for VIP to the right.(ABSTRACT TRUNCATED AT 250 WORDS)
Kamata
K
K
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Sakamoto
A
A
Kasuya
Y
Y
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000502:physiology*; D002918:Chymotrypsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000294:innervation*; D014660:Vasoactive Intestinal Peptide / Q000276:immunology / Q000494:pharmacology*
D001030:Apamin; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D002918:Chymotrypsin; D007545:Isoproterenol; D009638:Norepinephrine