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M L Dubocovich

Publications and source records attributed to M L Dubocovich.

14 recordsLinked to original sources
PubMed1992

Optic nerve transection decreases 2-[125I]iodomelatonin binding in the chick optic tectum.

The distribution of specific 2-[125I]iodomelatonin binding sites in the various layers of the chick optic tectum was analyzed using quantitative receptor autoradiography. Following unilateral optic nerve transection, binding in the optic fiber layer and superficial retinorecipient layers of the contralateral tectum was significantly decreased at 7 and 14 days, but not at 1 day, following transection. The results are consistent with the presence of presynaptic melatonin receptors on axon terminals of retinotectal fibers.

Animals↗
PubMed1979

Angiotensin II facilitates the potassium-evoked release of 3H-noradrenaline from the rabbit hypothalamus.

Antiotensin II facilitated in a concentration-dependent manner the potassium-evoked 3H-noradrenaline over-flow from the rabbit hypothalamus. This effect which is probably mediated through presynaptic angiotensin facilitatory receptors on noradrenergic nerve terminals was blocked by the specific angiotensin receptor antagonist, saralasin. These results demonstrate that angiotensin II also facilitates the stimulation-evoked release of noradrenaline in the central nervous system.

Angiotensin II↗
PubMed1978

Stimulation of presynaptic beta-adrenoceptors enhances [3H]-noradrenaline release druing nerve stimulation in the perfused cat spleen.

1 The effects of isoprenaline, propranolol and phosphodiesterase inhibitors on (3)H-transmitter overflow elicited by low frequency nerve stimulation were determined in the isolated perfused spleen of the cat.2 (-)-Isoprenaline (0.14, 1.4, and 14 nM) produced a concentration-dependent increase in [(3)H]-transmitter overflow evoked by nerve stimulation at 1 Hz and was more effective at 1 Hz than at 2 hertz.3 A concentration of propranolol (0.1 muM), devoid of neurone blocking activity, blocked this effect of (-)-isoprenaline. These results are compatible with the presence of beta-adrenoceptors in the noradrenergic nerve endings of the cat spleen.4 (+)-Isoprenaline (140 nM) failed to increase the release of radioactivity induced by nerve stimulation, indicating that the beta-adrenoceptor mediating the facilitation of transmitter release was stereospecific.5 The increase in (3)H-transmitter overflow induced by nerve stimulation during exposure to the phosphodiesterase inhibitor, papaverine (27 muM) was more pronounced than that obtained in the presence of 3-isobutyl-1-methyl xanthine (IBMX) 0.5 mM. The facilitation in transmitter release induced by papaverine was not correlated with the granular effect produced by this drug.6 In the presence of papaverine, the concentration-effect curve for (-)-isoprenaline on transmitter release was shifted to the left and its maximum was increased. In addition, propranolol significantly reduced the enhancement in noradrenaline release obtained by exposure to papaverine under conditions in which the granular effect produced by the phosphodiesterase inhibitor was even greater than in the absence of the beta-blocker.7 It is concluded that activation of presynaptic beta-adrenoceptors in the perfused cat spleen leads to an enhancement in transmitter release which appears to be linked to an increase in cyclic adenosine 3',5'-monophosphate levels in noradrenergic nerve endings.

Animals↗
PubMed1976

Influence of the frequency of nerve stimulation on the metabolism of 3H-norepinephrine released from the perfused cat spleen: differences observed during and after the period of stimulation.

The metabolism of 3H-norepinephrine (3H-NE) released by different frequencies of nerve stimulation was studied in the perfused cat spleen after labeling the endogenous stores with (-)-3H-NE. For a wide range of frequencies of stimulation, unmetabolized 3H-NE represented between 50 and 60% of the total increase in outflow of radioactivity elicited by nerve stimulation. The deaminated glycol, 3,4-dihydroxyphenylglycol (3H-DOPEG), was the main metabolite of 3H-NE released by nerve stimulation. When the increase in outflow of radioactivity was analyzed for the samples collected during nerve stimulation, there was a progressive decrease in the fraction of 3H-NE released which was collected as 3H-metabolites as the frequency of stimulation was increased from 0.5 to 5 Hz. For the samples collected in the poststimulation period, there was no frequency dependence in the metabolism of the released transmitter: approximately 75% of the total overflow of radioactivity was accounted for by the 3H-NE metabolites, particularly 3H-DOPEG. The time course of the metabolism of 3H-NE released by nerve stimulation revealed that 3H-DOPEG formation was rather small during stimulation and that it increased sharply in the poststimulation samples. The selective increase in 3H-DOPEG formation in the poststimulation period is compatible with the view that neuronal uptake of the released transmitter might be increased immediately after nerve stimulation. Inhibition of neuronal uptake by cocaine or by phenoxybenzamine prevented 3H-DOPEG formation from 3H-NE released by nerve stimulation. Yet, in the presence of cocaine, the fractional release of total radioactivity per shock was not increased at either 1, 5 or 30 Hz. These results support the view that a large fraction of the 3H-NE released by stimulation which is recaptured by nerve endings is metabolized to 3H-DOPEG rather than stored for subsequent reuse. The extensive conversion to 3H-DOPEG of 3H-NE released by nerve stimulation suggests that there may be a difference between the process of neuronal uptake under resting conditions and that which operates under conditions of nerve stimulation. This difference may be related to the concentration of the transmitter achieved in the synaptic gap in each experimental condition. Under resting conditions and during perfusion with low concentrations of NE, neuronal uptake in the perfused cat spleen is coupled with vesicular storage. On the other hand, when the extracellular concentration of NE is increased as a result of nerve stimulation, neuronal uptake of NE appears to be coupled with presynaptic metabolism through monoamine oxidase and aldehyde reductase.

Animals↗
PubMed1975

Evidence against a physiological role of prostaglandins in the regulation of noradrenaline release in the cat spleen.

1. The effects of prostaglandins E2 (PGE2) and indomethacin on responses and on noradrenaline overflow elicited by nerve stimulation were studied in the perfused cat's spleen, at different calcium concentrations in the perfusion medium: 0-26, 0-65 and 2-6 mve stimulation and in the overflow of the transmitter. PGE2 was more effective in reducing transmitter overflow at 5 than at 30 Hz. 3. Indomethacin, 14-0 muM, prevented the release of PGE-like material in the venous effluent of the spleen elicited by either nerve stimulation or by exogenous noradrenaline. 4. During exposure to 14-0 muM indomethacin there was no increase in responses to nerve stimulation or in the overflow of noradrenaline elicited by nerve stimulation at 5 or at 30 Hz. 5. Similar results to those obtained with exogenous PGE2 and with indomethacin in the presence of 2-6 mM calcium, were observed when the experiments were carried out in the presence of either 0-65 or 0-26 mM calcium. 6. In the presence of the alpha-adrenoceptor blocking agents, phenoxybenzamine (2-9 muM) or phentolamine (3-1 muM), the increase in transmitter overflow obtained during stimulation was 6-5 and 8-3-fold respectively. 7. Since inhibition of the synthesis of PGE did not increase transmitter overflow during nerve stimulation, it appears that the proposed negative feed-back mechanism mediated by endogenous prostaglandins does not play an important physiological role in the regulation of adrenergic neurotransmission in the cat spleen. In this tissue the major endogenous negative feed-back regulatory mechanism is triggered by the neurotransmitter through the activation of prejunctional alpha-adrenoceptors.

Animals↗