Presynaptic Neuromuscular Inhibition by Porphobilinogen and Porphobilin

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1971 Feb 1

PMID 4322608

Citations 12

Authors

D S Feldman

R D Levere

J S Lieberman

R A Cardinal

C J Watson

Affiliations

Soon will be listed here.

Abstract

The rat hemidiaphragm was studied in vitro as a test system to evaluate the effects of heme precursors and the uroporphyrins upon neuromuscular excitability. Porphobilinogen and porphobilin had no effect on the resting miniature end-plate potential frequency, but the K(+)-augmented frequency was significantly reduced. Porphobilin and porphobilinogen gave 50% of their maximal effect at concentrations of 0.008 and 0.6 mug/ml, respectively; the effect increased with concentration. Uroporphyrin I at 0.05-1.0 mug/ml caused a 25% decrease in frequency, but the effect did not increase with concentration. At similar concentrations, uroporphyrin III was without effect. The concentrations of porphobilin and porphobilinogen effective in inhibiting the K(+) stimulation, which are several orders of magnitude lower than the effective concentrations of simple amino acids, are those which might reasonably be expected in the sera of patients with acute intermittent porphyria.

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References

ELMQVIST D, Feldman D . Effects of sodium pump inhibitors on spontaneous acetylcholine release at the neuromuscular junction. J Physiol. 1965; 181(3):498-505. PMC: 1357662. DOI: 10.1113/jphysiol.1965.sp007778. View

Gage P, HUBBARD J . Evidence for a Poisson distribution of miniature end-plate potentials and some implications. Nature. 1965; 208(5008):395-6. DOI: 10.1038/208395a0. View

DAVIDOFF R, Shank R, Graham Jr L, Aprison M, WERMAN R . Association of glycine with spinal interneurones. Nature. 1967; 214(5089):680-1. DOI: 10.1038/214680a0. View

Kosower N, Rock R . Seizures in experimental porphyria. Nature. 1968; 217(5128):565-7. DOI: 10.1038/217565a0. View

Cardinal R, Bossenmaier I, Petryka Z, Johnson L, Watson C . Isolation of porphyrins from porphyria urine by preparative thin-layer chromatography. J Chromatogr. 1968; 38(1):100-5. DOI: 10.1016/0021-9673(68)85012-5. View

Feldman D, Levere R, Lieberman J . Presynaptic neuromuscular inhibition by delta-aminolevulinic acid, a porphyrin precursor. Trans Am Neurol Assoc. 1968; 93:206-8. View

HEILMEYER L, CLOTTEN R . [Biochemical pathogenesis of acute intermittent porphyria]. Klin Wochenschr. 1969; 47(2):71-4. DOI: 10.1007/BF01745768. View

TADDEINI L, Watson C . The clinical porphyrias. Semin Hematol. 1968; 5(4):335-69. View

STRAND L, Felsher B, Redeker A, MARVER H . Heme biosynthesis in intermittent acute prophyria: decreased hepatic conversion of porphobilinogen to porphyrins and increased delta aminolevulinic acid synthetase activity. Proc Natl Acad Sci U S A. 1970; 67(3):1315-20. PMC: 283354. DOI: 10.1073/pnas.67.3.1315. View

10.

FATT P, Katz B . An analysis of the end-plate potential recorded with an intracellular electrode. J Physiol. 1951; 115(3):320-70. PMC: 1392060. DOI: 10.1113/jphysiol.1951.sp004675. View

11.

GOLDBERG A, Paton W, Thompson J . Pharmacology of the porphyrins and porphobilinogen. Br J Pharmacol Chemother. 1954; 9(1):91-4. PMC: 1509378. DOI: 10.1111/j.1476-5381.1954.tb00822.x. View

12.

COOKSON G, Rimington C . Porphobilinogen. Biochem J. 1954; 57(3):476-84. PMC: 1269786. DOI: 10.1042/bj0570476. View

13.

Mauzerall D, Granick S . The occurrence and determination of delta-amino-levulinic acid and porphobilinogen in urine. J Biol Chem. 1956; 219(1):435-46. View

14.

LILEY A . The quantal components of the mammalian end-plate potential. J Physiol. 1956; 133(3):571-87. PMC: 1359121. DOI: 10.1113/jphysiol.1956.sp005610. View

15.

De Matteis F, Rimington C . The biochemical disturbance in acute intermittent and experimental porphyria. Lancet. 1962; 1(7243):1332-4. DOI: 10.1016/s0140-6736(62)92427-3. View

16.

Watson C, RUNGE W, TADDEINI L, Bossenmaier I, Cardinal R . A SUGGESTED CONTROL GENE MECHANISM FOR THE EXCESSIVE PRODUCTION OF TYPES I AND 3 PORPHYRINS IN CONGENITAL ERYTHROPOIETIC PORPHYRIA. Proc Natl Acad Sci U S A. 1964; 52:478-85. PMC: 300302. DOI: 10.1073/pnas.52.2.478. View

17.

Granick S, Levere R . HEME SYNTHESIS IN ERYTHROID CELLS. Prog Hematol. 1964; 4:1-47. View

18.

Katz B, Miledi R . THE EFFECT OF CALCIUM ON ACETYLCHOLINE RELEASE FROM MOTOR NERVE TERMINALS. Proc R Soc Lond B Biol Sci. 1965; 161:496-503. DOI: 10.1098/rspb.1965.0017. View

19.

ELMQVIST D, QUASTEL D . PRESYNAPTIC ACTION OF HEMICHOLINIUM AT THE NEUROMUSCULAR JUNCTION. J Physiol. 1965; 177:463-82. PMC: 1357260. DOI: 10.1113/jphysiol.1965.sp007605. View