Biomaterial Database

Effects of cocaine on excitation-contraction coupling of aortic smooth muscle from the ferret. 1991

K Egashira, and K G Morgan, and J P Morgan

Charles A. Dana Research Institute, Harvard-Thorndike Laboratory of Beth Israel Hospital, Boston, Massachusetts 02215.

The mechanism by which cocaine alters vascular tone is not fully understood. We determined the effects of cocaine on excitation-contraction coupling of isolated ferret aorta. Cocaine in concentrations less than or equal to 10(-4) M caused a contractile response in a dose-dependent manner. The response of control muscle was significantly larger than that in muscle from ferrets pretreated with reserpine. Cocaine-induced contraction was not affected by endothelial factors, but was significantly inhibited by prazosin 10(-7) M pretreatment. The intracellular calcium [( Ca++]i), as measured with aequorin, rose in conjunction with cocaine-induced contraction. The degree of contraction generated by 10(-4) M cocaine decreased after higher concentrations of cocaine greater than or equal to 10(-3) M, while aequorin luminescence remained elevated above the levels before 10(-6) M cocaine. The dose-response relationships of norepinephrine and sympathetic nerve stimulation were enhanced by 10(-6) M cocaine in control muscles; this did not occur in muscles from reserpine pretreated ferrets. In conclusion, (a) cocaine in concentrations less than or equal to 10(-4) M caused vascular contraction presumably by its presynaptic action with consequent alpha-1 adrenoceptor activation and consequent [Ca++]i rise; (b) high concentrations of cocaine greater than or equal to 10(-3) M reduced muscle tone by decreasing the Ca++ sensitivity of the contractile proteins; and (c) supersensitivity to norepinephrine was mediated by cocaine's action on adrenergic nerve endings.

UI	MeSH Term	Description	Entries
D009119	Muscle Contraction	A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.	Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009131	Muscle, Smooth, Vascular	The nonstriated involuntary muscle tissue of blood vessels.	Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D009638	Norepinephrine	Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic.	Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D011224	Prazosin	A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION.	Furazosin,Minipress,Pratsiol,Prazosin HCL,Prazosin Hydrochloride,HCL, Prazosin,Hydrochloride, Prazosin
D012110	Reserpine	An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.	Raunervil,Raupasil,Rausedil,Rausedyl,Serpasil,Serpivite,V-Serp,V Serp
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D003042	Cocaine	An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.	Cocaine HCl,Cocaine Hydrochloride,HCl, Cocaine,Hydrochloride, Cocaine
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004730	Endothelium, Vascular	Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.	Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D005289	Ferrets	Semidomesticated variety of European polecat much used for hunting RODENTS and/or RABBITS and as a laboratory animal. It is in the subfamily Mustelinae, family MUSTELIDAE.	Domestic Polecat,Domestic Polecats,European Polecat,European Polecats,Ferret,Mustela putorius,Mustela putorius furo,Polecat, Domestic,Polecat, European,Polecats, Domestic,Polecats, European