ABSTRACT
Dopamine deficiency is characteristic of Parkinson's disease (PD) and treatments aim at elevating levels by administration of its precursor L-dihydroxyphenylalanine (L-DOPA), or inhibiting monoamine oxidases (MAOs), thus preventing its breakdown. Reports of improvements in PD patients treated with Banisteriopsis caapi extracts stimulated investigation of B. caapi stem extract and its two ingredients, harmine and harmaline for these activities. Tests for MAO inhibition using liver homogenate showed that extract and harmaline showed a concentration-dependent inhibition of MAO A (IC(50) 1.24 microg/ml and IC(50) 4.54 nM, respectively) but had little effect on MAO B activity. The extract at 2.5 mg/ml caused a highly significant increase in release of [3H]dopamine from rat striatal slices, as did 200 microM harmine and 6 microM harmaline. In both these experiments, the amount of harmine present could not account for the total activity of the extract. The ability of harmine and harmaline to stimulate dopamine release is a novel finding. These results give some basis to the reputed usefulness of B. caapi stem extract in the treatment of PD.
Subject(s)
Banisteriopsis , Enzyme Inhibitors/therapeutic use , Parkinson Disease/drug therapy , Plant Stems , Animals , Corpus Striatum/drug effects , Corpus Striatum/enzymology , Corpus Striatum/metabolism , Dopamine/metabolism , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Liver/drug effects , Liver/enzymology , Liver/metabolism , Male , Monoamine Oxidase/metabolism , Parkinson Disease/enzymology , Parkinson Disease/metabolism , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Rats , Rats, WistarABSTRACT
The relationship between blood pressure and platelet basal cytoplasmic calcium concentration ([Ca2+]i) and platelet sensitivity to aggregating agents in hypertension has been investigated in hypertensive patients and normotensive subjects. Ten severely hypertensive patients whose blood pressures were poorly controlled with metoprolol, were given calcium antagonist (either nifedipine or felodipine) as a second line agent. Venous blood samples were collected at each treatment phase for measurement, in whole blood, of platelet aggregation in response to ADP and collagen, and of basal [Ca2+]i using fura-2. Control of blood pressure by the combination of metroprolol and a calcium antagonist induced a significant decrease in median [Ca2+]i from 116 (76-181) to 73 (60-83) nM, which was similar to the median value of 70 (61-80) nM obtained in 14 normotensive subjects. Overall [Ca2+]i correlated with mean blood pressure (r = 0.51). Treatment of hypertension with calcium antagonist did not change the response of platelets to collagen or ADP. The results confirm that effective treatment of hypertension significantly reduced basal [Ca2+]i in platelets but raise doubts whether elevated basal [Ca2+]i is necessarily the sole mechanism by which the sensitivity of platelets to aggregatory agents is increased in hypertension.
Subject(s)
Blood Platelets/drug effects , Calcium/blood , Cytoplasm/metabolism , Hypertension/drug therapy , Platelet Aggregation/drug effects , Adult , Aged , Basal Metabolism , Blood Platelets/metabolism , Blood Pressure/drug effects , Drug Therapy, Combination , Felodipine/administration & dosage , Female , Humans , Male , Middle Aged , Nifedipine/administration & dosage , Sensitivity and SpecificityABSTRACT
Incubation of platelet-rich plasma (PRP) with ouabain, an inhibitor of sodium/potassium ATPase (Na+/K+ ATPase), induced a significant rise in basal platelet intracellular calcium concentration [( Ca2+]i) when measured using fura 2. Ouabain induced an enhanced aggregation response to low doses of collagen in both PRP and washed platelets loaded with aequorin. In aequorin loaded platelets this enhanced aggregation response was associated with an enhanced rise in [Ca2+]i such that the relationship between [Ca2+]i and aggregation was unchanged. As inhibition of plasma membrane Na+/K+ ATPase would lead to a raised intracellular sodium ion concentration [( Na+]i) the results suggest that in the platelet, [Na+]i can modulate [Ca2+]i and hence influence the response of platelets to stimuli such as collagen.
Subject(s)
Blood Platelets/analysis , Calcium/analysis , Ouabain/pharmacology , Blood Platelets/drug effects , Collagen/pharmacology , Cyclic AMP/physiology , Cytoplasm/analysis , Humans , Platelet Aggregation/drug effects , Potassium/analysis , Sodium/physiologyABSTRACT
The location of the photoperiodic mechanism controlling the production of the sexual and parthenogenetic morphs by apterous parents was examined by selectively injuring the brain with an R.F. microcautery. Lesions destroying the Group I neurosecretory cells (NSC) in the protocerebrum abolished the response to changed daylength. Extensive damage to other NSC Groups, to the compound eyes and optic lobes was without effect. It is concluded that the Group I NSC are the effectors, secreting a virginoparapromoting substance; in its absence only oviparae are produced. Areas slightly lateral to the group I NSC are also required for the long-day response, indicating that this is the probable site of the neuronal photoperiodic clock which regulates the release of neurosecretory material (NSM) from the Group I cells.