Accumulation of 1-methyl-4-phenylpyridinium (MPP+) into bovine chromaffin granules results in a large restriction of its molecular motion: a 13C and 31P NMR study.
13C labelled 1-methyl-4-phenylpyridinium ([13C-methyl]MPP+) is taken up by chromaffin granules and a signal from the methyl group within the granular matrix appears at 49.8 ppm. No shift of the [13C-Me] signal is observed upon incorporation into the granules. However the linewidth of the signal is significantly increased suggesting a restriction in the molecular motion of MPP+. Confirmation of the above derives from the determination of the T1 relaxation time of the [13C-Me] carbon of MPP+ which shows a four fold decrease upon incorporation of MPP+ into the granule. 31P NMR spectra of ATP in the presence of MPP+ reveals that the toxicant has low affinity for the nucleotide, suggesting that it is the viscosity of the granular matrix that restricts MPP+ mobility rather than a specific interaction with intragranular ATP.
Daniels
A J
AJ
Division of Medicinal Biochemistry, Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.
Reinhard
J F
JF
Painter
G R
GR
D015655:1-Methyl-4-phenylpyridinium; D000255:Adenosine Triphosphate / Q000378:metabolism; D000313:Adrenal Medulla / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002837:Chromaffin Granules / Q000378:metabolism*; D002838:Chromaffin System / Q000378:metabolism*; D004735:Energy Transfer; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D011726:Pyridinium Compounds / Q000493:pharmacokinetics*; D014783:Viscosity
D011726:Pyridinium Compounds; D000255:Adenosine Triphosphate; D015655:1-Methyl-4-phenylpyridinium