Choline acetyltransferase activity in rat heart after transplantation

Lund, Donald D.; Schmid, Phillip G.; Kelley, Stephen E.; Corry, Robert J.; Roskoski, Robert

doi:10.1152/ajpheart.1978.235.4.h367

Cited by 9 publications

(6 citation statements)

References 16 publications

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“…The very low binding of ( -)FEOBV in ventricles in comparison to the uptake and retention of other cardiac PET tracers will likely impede its application in viva In light of in vitro studies showing high affinity of benzovesamicol derivatives to the vesicular acetylcholine transporter (Rogers et al, 1989), the present study suggests that the slow rate of binding of the tracer within tissue is primarily due to a very low concentration of the transporter in the tissue. This is consistent with a low density of cholinergic innervation of the heart (Lund et al, 1978;Slavikova and Tucek, 1982). Thus, the uptake and clearance patterns of ( -)FEOBV in the myocardium determined from external monitoring are largely dependent on uptake and turnover of tracer from non-specific sites.…”

Section: Totalsupporting

confidence: 79%

“…The extensive clearance of "F in the wash-out phase indicates a high fraction (> 90%) of the initial ( -)FEOBV accumulation to be freely diffusible. The low retention of radiotracer by the heart is consistent with a low density of cholinergic neurons (Lund et al, 1978;Slavikova and Tucek, 1982) possessing specific vesamicol binding sites. The possibility of competitive inhibition of (-)FEOBV binding at the vesicular acetylcholine transporter by non-radioactive material in the radiopharmaceutical preparations is unlikely with the HPLC purified, no-carrier-added "F-labeled radiotracers utilized in this work.…”

Section: Discussionsupporting

confidence: 54%

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Evaluation of ( − )[18F]fluoroethoxybenzovesamicol as a new PET tracer of cholinergic neurons of the heart

DeGrado

Mulholland

Wieland

et al. 1994

Nuclear Medicine and Biology

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18F-labeled (-)fluoroethoxybenzovesamicol [(-)FEOBV] is a novel PET tracer which binds to the vesicular acetylcholine transporter of cholinergic neurons. To evaluate the in vivo binding specificity and kinetic properties of (-)FEOBV, studies were performed in isolated working rat hearts. External gamma,gamma-coincidence monitoring of hearts indicated high extraction of radiotracer by the myocardium and rapid wash-out of unbound tracer (> 90% of maximal accumulation) within 5 min. Inclusion of (-)vesamicol (10 microM) throughout perfusion decreased the retention of (-)FEOBV by 71% (P < 0.005) and 76% (P < 0.005) in atria and ventricles, respectively. However, the initial uptake rate of the tracer was unaffected. Additional experiments showed the inactive stereoisomer, (+)FEOBV, to have a lower retention than the (-)FEOBV isomer in ventricles, indicating stereospecificity of the binding process that is consistent with structure-activity relationships of vesamicol congeners. The results indicate (-)FEOBV to be a moderately specific probe of vesamicol-sensitive binding in cholinergic neurons of the heart in experimental conditions that assure adequate washout of unbound tracer. However, the utility of the radiotracer for in vivo studies with PET is likely to be limited by the low rate of specific binding in myocardium consistent with the low density of cholinergic neurons in the heart.

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Section: Totalsupporting

confidence: 79%

Section: Discussionsupporting

confidence: 54%

Evaluation of ( − )[18F]fluoroethoxybenzovesamicol as a new PET tracer of cholinergic neurons of the heart

DeGrado

Mulholland

Wieland

et al. 1994

Nuclear Medicine and Biology

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“…With regard to our neurochemical findings, CAT activity is a reliable index of parasympathetic, cholinergic innervation of the heart (15)(16)(17). When interpreting CAT activity data, it is important to consider how the data are expressed.…”

Section: Discussionmentioning

confidence: 99%

“…CAT activity was measured by a radiochemical assay as previously described (15)(16)(17) CAT activity was measured as a concentration in each heart chamber (nmol • g~1 • h~1). Because of differences in heart weights between the control and diabetic rats, the data were corrected by calculating the total CAT content per chamber (nmol/chamber per h).…”

Section: Methodsmentioning

confidence: 99%

Alterations in Cardiac Parasympathetic Indices in STZ-Induced Diabetic Rats

Lund

Subieta²,

Pardini³

et al. 1992

Diabetes

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Autonomic neuropathy involving parasympathetic innervation is a complication of diabetes mellitus. Biochemical and morphological indices of the parasympathetic innervation of the heart were investigated in rats after diabetes mellitus was induced with streptozocin (STZ). Choline acetyltransferase (CAT) activity was used as a biochemical marker for parasympathetic innervation. Total CAT activity within the hearts of diabetic rats was unchanged after 1 and 2 wk of diabetes and was significantly reduced after 4, 8, and 12 wk. Morphological changes within the cardiac portion of the parasympathetic innervation were assessed at 8 wk when CAT activity was decreased. In diabetic rats, there was a reduction in both cardiac ganglion cell size and number. In contrast, in insulin-treated STZ-induced diabetic rats, ganglion cells were similar in size and number to those in a control group given 3-O-methylglucose to prevent induction of diabetes mellitus by STZ. Thus, diabetes mellitus is associated with alterations in cardiac parasympathetic innervation in rats, and supplemental insulin protects against these changes. These alterations may contribute to impaired parasympathetic neural control of the heart in diabetes mellitus.

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“…After complete interruption of vagal input, a rapid decrease in the biochemical markers of parasympathetic activity occurs (Brown, 1976;Lund et al, 1978Lund et al, , 1979. The fact that the application of physostigmine to atrial tissue following bilateral cervical vagotomy produces no effect provides a physiological correlate for the observation that vagotomy depletes tissue stores of acetylcholine.…”

Section: Discussionmentioning

confidence: 99%

Effects of acetylcholine on action potential characteristics of atrial and ventricular myocardium after bilateral cervical vagotomy in the cat.

Kovacs¹,

Bailey²

1985

Circulation Research

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Acetylcholine, the parasympathetic neurotransmitter, shortens the action potential duration of cat atrial muscle cells, but not ventricular muscle cells. In mammalian species, atrial tissue receives a richer cholinergic nerve supply than ventricular tissue. To determine whether chronic withdrawal of cholinergic tone might influence the subsequent response of these tissues to cholinergic stimulation, we examined the effect of acetylcholine on the action potentials of atrial and ventricular myocytes from cats with intact vagi and cats after chronic bilateral cervical vagotomy. Following bilateral cervical vagotomy, physostigmine (10(-6) M) failed to alter atrial tension development or action potential duration. Acetylcholine produced shortening of the action potential duration in atrial muscle from cats with intact vagi and in cats following bilateral cervical vagotomy. However, the degree of shortening produced by acetylcholine after bilateral cervical vagotomy was significantly greater (P less than 0.001). In ventricular muscle from cats with intact vagi, acetylcholine did not alter action potential duration. In ventricular muscle from cats after bilateral cervical vagotomy, acetylcholine shortened the action potential duration. Maximal effect was seen at a concentration of 10(-5) M where acetylcholine shortened action potential duration at 90% repolarization from a control value of 179 +/- 4 to 150 +/- 7 msec. Atropine (10(-6) M) reversed the effects of acetylcholine. Addition of propranolol (10(-6) M) to the superfusate or pretreatment of the animals with reserpine (2 mg/kg, ip) 24 hours before sacrifice failed to alter the response of ventricular muscle cells to acetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)

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Choline acetyltransferase activity in rat heart after transplantation

Cited by 9 publications

References 16 publications

Evaluation of ( − )[18F]fluoroethoxybenzovesamicol as a new PET tracer of cholinergic neurons of the heart

Evaluation of ( − )[18F]fluoroethoxybenzovesamicol as a new PET tracer of cholinergic neurons of the heart

Alterations in Cardiac Parasympathetic Indices in STZ-Induced Diabetic Rats

Effects of acetylcholine on action potential characteristics of atrial and ventricular myocardium after bilateral cervical vagotomy in the cat.

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