Pharmacological effects of haem biosynthetic intermediates in isolated intestinal preparations

Spontaneous contractile activity of isolated rabbit jejunal preparations bathed in oxygenated Ringer-Locke buffered to pH 7.0 was inhibited by haemin and by all haem biosynthetic intermediates tested, there being decreases in tone or amplitude of contractions. Effects were concentration-dependent. The minimal effective concentrations were 0.4 mM for porphobilinogen, 0.6 mM for protoporphyrin IX, 0.8 mM for haemin, 3.0 mM for delta-aminolaevulinic acid (ALA), 4.5 mM for coproporphyrin I, 3.0 mM for glycine and 6.0 mM for succinate. Inhibition was short-lasting, other than for protoporphyrin (2.3 mM) and haemin (3.0 mM). Leucine at concentrations up to 12 mM had no significant effect. Inhibitory effects of ALA were followed by contractions of increased amplitude; pretreatment of preparations with indomethacin (56 microM) prevented this enhancement of contractile activity. Tone in isolated preparations of human taenia coli bathed in oxygenated Ringer-Locke was decreased by ALA (1.5-6.0 mM). A significant increase of tone followed the initial inhibitory effect. The relevance of these findings to acute porphyria is discussed.