Effect of beta-casomorphins on intestinal propulsion in the guinea-pig colon.
beta-Casomorphins are a family of opioid peptides originally isolated from beta-casein. In view of a possible physiological significance of these milk-derived compounds, the effects of bovine beta-casomorphin-5 (beta-CM-5), beta-casomorphin-4 (beta-CM-4) and D-Ala2-beta-casomorphin-4-NH2 (D-Ala2-beta-CM-4-NH2) have been investigated on the peristaltic reflex in the guinea-pig isolated colon and compared with morphine. beta-CM-5 and D-Ala2-beta-CM-4-NH2 each dose-dependently inhibited the velocity of propulsion of an intraluminal bolus; beta-CM-4 was ineffective. IC50 values were 0.30, 5.21 and 0.29 microM for morphine, beta-CM-5 and D-Ala2-beta-CM-4-NH2, respectively. The potency ratios vs morphine were 0.06 and 0.96 for beta-CM-5 and D-Ala2-beta-CM-4-NH2, respectively. Blockade of the peristaltic reflex by beta-CM-5 or D-Ala2-beta-CM-4-NH2 was reversed by the opioid antagonist naloxone. D-Ala2-beta-CM-4-NH2 also dose-dependently inhibited resting acetylcholine output (IC50 = 5.69 microM; potency ratio vs morphine: 0.63). In conclusion, certain beta-casomorphins inhibit intestinal propulsion and cholinergic neurotransmission in the guinea-pig colon, probably by acting at opioid receptors.
De Ponti
F
F
Department of Internal Medicine and Therapeutics, University of Pavia, Italy.
Marcoli
M
M
Lecchini
S
S
Manzo
L
L
Frigo
G M
GM
Crema
A
A
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D003106:Colon / Q000187:drug effects*; D004723:Endorphins / Q000494:pharmacology*; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D010528:Peristalsis / Q000187:drug effects
D004723:Endorphins; D009294:Narcotics; D009270:Naloxone; C021968:beta-casomorphins; D000109:Acetylcholine