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“General Pharmacology and Cocaine-Induced Supersensitivity of Noninnervated-Guinea Pig:Umbilical Vasculature”.
Dissertation Abstrect. lntern. B.. 1974;35(1):413-14.
Cocaine-induced super-sensitivity in the noinnervated guinea pig umbilical blood vessels were studied. Pregnant albino Hartley guineapigs within1 wk of term were ane-sthetized. with pentobarbital (30 mg/kg) and supplemented if needed with ether. The umbilical blood vessels were excised and.the arterie's and.vein were:separated and helically-cut. Vein or artery strips were. suspended in isolated muscle baths at 37°. Tissues were equilibrated under a 500 mg-resting tension for 2 hr before drug-treatments. 5--Hydroxydryptamine - 3-l4C and 1-norepinephrine-7- 3H were used to determine the effect of cocaine, normetanephrine and desmethylimipra-mine on the accumulation of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) by the guinea pig umbilical vein. 45CaCl2 was used to determine the effect of cocaine on Ca++ ion uptake by the tissues.contracted with 5-HT (10-5M) or NE (to 5M). To establish:the pharmacological similarity of guinea pig and human umbilical-blood vessels.the:effect of various biogenic amines, polypepdides and hallucinogens were examined. The combined use of these agonists with antagonists such: as cinanserin, 2 - bromolysergic :acid diethylamide, tripelennamine, phenoxybenzamine, atropine and propranolol revealed the.presence of serotonergic, alpha and beta adrenergic,cholinergic and histaminergic receptor sites in these vessels. These blood vessels also contracted to angiotensin, bradykinin, lysergic acid diethylamide, mescaline, :psilocin and p-silocybin. Cocaine significantly enhanced themaximal response of.guinea.pig umbilical vein and artery to 5-HT, NE, Ach and agiontensin. The role of innibition of enzymatic degradation was studied using iproniazid (MAO-inhibitor) and tropolone (COMT inhibitor).
Iproniazid aid not alter contractions to 5-HT and NE; whereas tropolone slightly increased contractions to NE, but did not alter responses to NE in the. presence of cocaine. Chlorimipramine an inhibitor of 5-HT uptake. did not affect responses of tine guinea pig unbilical vein to 5-HT. Desmethylimipramine (DMI) only slightly increased response to 5 - HT (10- M) and-NE. The accumulation of 14C-5-Ht-and 3H-NE by umeumbilical vein was not alteredby normetanephrine, cocaine or DMI.-: Cocaine-induced.supersensitivity izicreased as the Ca++ concentration of the bath solution increased from 1 :mM to 3 mM. Procaine (10-0M) did not increase the maximal.response or the Ca++:uptake.into these tissues when stimulated with 5-HT or NE.
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