Manganese can inhibit or potentiate contractile responses in mesenteric portal vein.
The effects of a number of agents believed to interfere with Ca were examined on contraction induced by noradrenaline (NA) or K in rat mesenteric portal veins. The organic calcium antagonists nifedipine, verapamil, methoxyverapamil, and felodipine slowly produced maximum inhibitory effects, nifedipine being fastest with a T1/2 of 20 min. In contrast, the inhibitory effects of Mn were immediate but disappeared on continued exposure of the tissue to Mn. After removal of Mn from the bath fluid, an above normal contraction was produced by K or NA. Measurement of Mn by atomic absorption spectrometry showed that the concentrations of EDTA-resistant Mn increased in parallel with the loss of inhibitory effects of Mn. This is consistent with an external inhibitory effect of Mn but a potentiating effect of Mn once it reaches an EDTA-inaccessible site. The potentiating effect of Mn was not seen with other ions such as Cd, Ni, Co, Mg, and La, which produced only inhibition of responses to NA or K. Contractile responses to Ba were examined in the absence of external Ca and it was found that the responses decreased with time. The presence of Mn not only prevented the loss of contractility but produced a marked increase in the response to Ba. Relaxation rates were also studied and it was found that Mn speeds the relaxation of contractures produced by NA or Ba as long as Mn is present in the bath fluid, but Mn slows relaxation when it is present (presumably) intracellularly. Mn does not alter relaxation rates of K contractures.(ABSTRACT TRUNCATED AT 250 WORDS)
Sutter
M C
MC
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
May
P B
PB
Lim
S L
SL
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000037:antagonists & inhibitors; D015736:Felodipine; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008345:Manganese / Q000493:pharmacokinetics / Q000494:pharmacology*; D008642:Mesenteric Veins / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009568:Nitrendipine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013054:Spectrophotometry, Atomic; D013324:Strontium / Q000494:pharmacology; D014018:Tissue Distribution; D014700:Verapamil / Q000494:pharmacology
D001464:Barium; D005711:Gallopamil; D008345:Manganese; D009568:Nitrendipine; D014700:Verapamil; D009543:Nifedipine; D015736:Felodipine; D002118:Calcium; D013324:Strontium