T. Yamazaki et al., Dialysate dihydroxyphenylglycol as a window for in situ axoplasmic norepinephrine disposition, NEUROCHEM I, 38(3), 2001, pp. 287-292
To examine basal axoplasmic norepinephrine (NE) kinetics at the in situ car
diac sympathetic nerve ending, we applied a dialysis technique to the heart
of anesthetized cats and performed the dialysate sampling with local admin
istration of a pharmacological tool through a dialysis probe. The dialysis
probe was implanted in the left ventricular wall, and dihydroxyphenylglycol
(DHPG, an index of axoplasmic NE) levels were measured by liquid chromate
gram-electro chemical detection. Control dialysate DHPG levels were 161 +/-
19 pg/ml. Pargyline (monoamine oxidase inhibitor, 1 mM) decreased the dial
ysate DHPG levels to 38 +/- 10 pg/ml, Further alpha -methyl-para-tyrosine,
omega -conotoxin GVIA, desipramine (NE synthesis, release and uptake blocke
rs) decreased the dialysate DHPG levels to 64 +/- 19, 106 +/- 15, 110 +/- 2
2 pg/ml, respectively. In contrast, reserpine (vesicle NE transport inhibit
or, 10 muM) increased the dialysate DHPG levels to 690 +/- 42 pg/ml. Thus,
NE synthesis, metabolism and recycling (release, uptake and vesicle transpo
rt) affected basal intraneuronal NE disposition at the nerve endings. Measu
rement of DHPG levels through a dialysis probe provides information about b
asal intraneuronal NE disposition at the cardiac sympathetic nerve endings.
Yohimbine (alpha (2)-adrenoreceptor blocker, 10 muM) and U-521 (catechol-O
-methyltransferase blocker, 100 muM) did not alter the dialysate DHPG level
s. Furthermore, there were no significant differences in the reserpine indu
ced DHPG increment between the presence and absence of desipramine (10 muM)
or alpha -methyl-para-tyrosine (100 mg/kg i.p.). These results may be expl
ained by the presence of two axoplasmic pools of NE, filled by NE taken up
and synthesized, and by NE overflow from vesicle. The latter pool of NE may
be closed to the monoamine oxidase system in the axoplasma. (C) 2001 Elsev
ier Science Ltd. All rights reserved.