Pharmacological activities of delta-aminolaevulinic acid, protoporphyrin IX and haemin in isolated preparations of rabbit gastric fundus and jejunum.
1. Pharmacological effects of delta-aminolaevulinic acid (ALA), protoporphyrin IX and haemin were examined in isolated preparations of rabbit jejunum and gastric fundus suspended in oxygenated Ringer-Locke solution at pH 7.0. 2. In jejunal preparations, delta-aminolaevulinic acid (3.0-4.5 mM), protoporphyrin IX (1.1-2.2 mM) and haemin (3.0-4.5 mM) dose-dependently reduced the amplitude of contractions and increased resting length. Pretreatment with prazosin (10(-7) M) inhibited effects produced by delta-aminolaevulinic acid (3 mM) and protoporphyrin IX (1.1 mM) but not those of haemin (3 mM). 3. In fundic preparations, dose-dependent contracture occurred in response to delta-aminolaevulinic acid (0.1-3.0 mM) protoporphyrin IX (0.1-2.2 mM) and haemin (0.6-6.3 mM). Effects qualitatively resembled those of noradrenaline (0.1-0.4 microM). Prazosin (10(-7) M) attenuated these effects, depressing the maximum response and causing a rightward shift of the concentration-response curves. 4. It is concluded that actions of delta-aminolaevulinic acid at alpha 1-adrenoceptor sites are unlikely to be related to the autonomic neuropathy of acute porphyria. Its in vitro effects occurred only at comparatively high concentrations and were mimicked by protoporphyrin IX and haemin. It is suggested that ALA is more likely to modify autonomic functions by an indirect action, since it is known at low dose levels to influence GABA-ergic functioning.
Cutler
M G
MG
Department of Biological Sciences, Glasgow College, UK.
Mair
J
J
Moore
M R
MR
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D005260:Female; D005748:Gastric Fundus / Q000187:drug effects; D006418:Heme / Q000031:analogs & derivatives*; D006427:Hemin / Q000494:pharmacology*; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects; D007982:Levulinic Acids / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011166:Porphyrins / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology*; D011817:Rabbits
D007982:Levulinic Acids; D011166:Porphyrins; D011524:Protoporphyrins; D006418:Heme; D006427:Hemin; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D011224:Prazosin