The role of intracellular calcium stores in motilin induced contractions of the longitudinal muscle of the rabbit duodenum.
The contraction of longitudinal muscle strips of the rabbit duodenum in response to motilin and acetylcholine was investigated in normal and high K+-solutions in the presence and absence of external calcium, in order to demonstrate the existence of pharmaco-mechanical coupling for motilin and to examine whether the peptide mobilizes calcium from an intracellular store. In depolarized smooth muscle (140 mM K+), motilin (3.2 x 10(-9)-1 x 10(-7) M) and acetylcholine (1 x 10(-5) M) were still capable of causing a considerable, transient, concentration-dependent contraction in the presence of Ca2+. The 'extra'-contraction to motilin was not blocked by tetrodotoxin (1 microgram/ml) nor by atropine (10(-7) M), but acetylcholine (10(-5) M) was blocked by atropine. Verapamil (10(-7) M) could selectively block the K+ contraction without affecting the extra agonist contraction. Nitroprusside was ineffective up to 10(-4) M in high K+-solutions, but in normal Hepes-buffer it caused a concentration-dependent rightward shift of the concentration-response curve of motilin and acetylcholine contractions. In a calcium-depleted medium, high K+-depolarized muscle strips were still responsive to motilin and acetylcholine, but higher concentrations (10(-6) M) were needed than in the presence of calcium and the contractions reached only 57 +/- 11% and 74 +/- 9% respectively of the maximal contraction in 1.2 mM Ca2+ containing solutions. The response to motilin (10(-6) M) was not only smaller than that to acetylcholine (10(-5) M), it also faded more rapidly with time.(ABSTRACT TRUNCATED AT 250 WORDS)
Matthijs
G
G
Gastroenterological Research, University of Leuven, Belgium.
Peeters
T L
TL
Vantrappen
G
G
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D004386:Duodenum / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009037:Motilin / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D009599:Nitroprusside; D013779:Tetrodotoxin; D009037:Motilin; D001285:Atropine; D014700:Verapamil; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium