Biomaterial Database

Neomycin and omega-conotoxin GVIA interact at a common neuronal site in peripheral tissues. 1990

R A Keith, and D LaMonte, and A I Salama

ICI Pharmaceuticals, ICI America Inc., Wilmington, Delaware 19897.

1. The present study examined the interaction of omega-conotoxin GVIA (omega-CT) and aminoglycoside antibiotics on electrically evoked, nerve-mediated contractile responses in the rat vas deferens, guinea-pig ileum and guinea-pig left atria. 2. omega-CT caused a time- and concentration-dependent inhibition of the electrically evoked twitch responses of the rat vas deferens and guinea-pig ileum. Aminoglycoside antibiotics inhibited the twitch responses of these preparations with a rank order of potency: neomycin greater than gentamycin greater than kanamycin. omega-CT had no effect on the postjunctional contractile responses of either noradrenaline (vas deferens) or carbachol (ileum). However, at high concentrations neomycin and gentamycin caused significant postjunctional inhibition. The results suggest that omega-CT and aminoglycosides cause prejunctional inhibition in these preparations, with the aminoglycoside antibiotics exhibiting postjunctional inhibitory effects as well at high concentrations. 3. omega-CT caused a concentration- and frequency-dependent inhibition of the neuronally mediated field stimulation enhancement of electrically paced guinea-pig left atria. omega-CT had no effect on either the electrically paced contractile response that was elicited by direct muscle stimulation or the enhancement of the paced response caused by beta-adrenoceptor agonist stimulation. Neomycin caused a concentration-dependent inhibition of the electrically paced contractile response and inhibited the field stimulation response only at concentrations which caused pronounced inhibition of the paced response. Neomycin also caused insurmountable inhibition of responses elicited by beta-adrenoceptor agonist stimulation. Thus, omega-CT caused an exclusive prejunctional inhibition in guinea-pig left atria, whereas the substantial postjunctional effects of neomycin made it difficult to discern any prejunctional activity of neomycin in these experiments. 4. In the vas deferens, ileum and atria the inhibitory effects of omega-CT were long-lasting, whereas the effects of neomycin could be reversed upon wash-out. The disparate kinetics of omega-CT and neomycin allowed for the design of receptor protection studies to determine whether neomycin acts at a prejunctional site in common with omega-CT. The pre-equilibration of a competitive antagonist (neomycin) should prevent the irreversible antagonist (omega-CT) from gaining access to receptors. Pre-exposure of tissues with neomycin prevented the irreversible inhibition of omega-CT. These receptor protection studies suggest that omega-CT and neomycin interact at common neuronal sites in the rat vas deferens, guinea-pig ileum and guinea-pig atria. Neomycin, however, exhibits activity at postjunctional sites as well.

UI	MeSH Term	Description	Entries
D008978	Mollusk Venoms	Venoms from mollusks, including CONUS and OCTOPUS species. The venoms contain proteins, enzymes, choline derivatives, slow-reacting substances, and several characterized polypeptide toxins that affect the nervous system. Mollusk venoms include cephalotoxin, venerupin, maculotoxin, surugatoxin, conotoxins, and murexine.	Conus Venoms,Octopus Venoms,Snail Venoms,Conus Venom,Mollusc Venoms,Mollusk Venom,Octopus Venom,Snail Venom,Venom, Conus,Venom, Mollusk,Venom, Octopus,Venom, Snail,Venoms, Conus,Venoms, Mollusc,Venoms, Mollusk,Venoms, Octopus,Venoms, Snail
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
D009130	Muscle, Smooth	Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)	Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D009355	Neomycin	Aminoglycoside antibiotic complex produced by Streptomyces fradiae. It is composed of neomycins A, B, and C, and acts by inhibiting translation during protein synthesis.	Fradiomycin Sulfate,Neomycin Palmitate,Neomycin Sulfate
D009469	Neuromuscular Junction	The synapse between a neuron and a muscle.	Myoneural Junction,Nerve-Muscle Preparation,Junction, Myoneural,Junction, Neuromuscular,Junctions, Myoneural,Junctions, Neuromuscular,Myoneural Junctions,Nerve Muscle Preparation,Nerve-Muscle Preparations,Neuromuscular Junctions,Preparation, Nerve-Muscle,Preparations, Nerve-Muscle
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010456	Peptides, Cyclic	Peptides whose amino acid residues are linked together forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS; some are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).	Circular Peptide,Cyclic Peptide,Cyclic Peptides,Cyclopeptide,Orbitide,Circular Peptides,Cyclopeptides,Orbitides,Peptide, Circular,Peptide, Cyclic,Peptides, Circular
D011943	Receptors, Adrenergic, beta	One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.	Adrenergic beta-Receptor,Adrenergic beta-Receptors,Receptors, beta-Adrenergic,beta Adrenergic Receptor,beta-Adrenergic Receptor,beta-Adrenergic Receptors,Receptor, Adrenergic, beta,Adrenergic Receptor, beta,Adrenergic beta Receptor,Adrenergic beta Receptors,Receptor, beta Adrenergic,Receptor, beta-Adrenergic,Receptors, beta Adrenergic,beta Adrenergic Receptors,beta-Receptor, Adrenergic,beta-Receptors, Adrenergic
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D004558	Electric Stimulation	Use of electric potential or currents to elicit biological responses.	Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical