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Biomedical subjects

M Nirenberg

Publications and source records attributed to M Nirenberg.

At least 73 records · Page 4Linked to original sources
PubMed1978

Pharmacologic responses of cells of a neuroblastoma X glioma hybrid clone and modulation of synapses between hybrid cells and mouse myotubes.

Cells of the hybrid clone NG108-15 responded to 5-hydroxytryptamine (5-HT), dopamine or acetylcholine with graded depolarizations involving membrane conductance increases. Responses desensitized during continuous application of the neurotransmitters, and responses to 5-HT and dopamine cross-desensitized: a desensitizing application of one neurotransmitter also desensitized the hybrd cell to the other neurotransmitter. 5-HT and acetylcholine did not cross-desensitize. The hybrid cell 5-HT response was not attenuated by D-LSD, and was blocked by 10(-5) M morphine, although not via binding to naloxone-sensitive opiate receptors. 5-HT or the prostaglandin PGF2alpha caused the release of acetylcholine at the synapses of hybrid cells with mouse myotubes. Application of 5-HT or PGF2alpha also facilitated the synaptic release elicited by hybrid cell action potentials. Following treatment with the antimitotic agent cytosine arabinoside, co-cultures of hybrid cells and mouse myotubes exhibited plentiful synaptic connections only if maintained in medium containing 1 mM dibutyryl cAMP (dBcAMP). After X-irradiation, co-cultures were synaptically active even in the absence of dBcAMP. Thus, methods have been found to regulate both the short-term and long-term synaptic activity of NG108-15 hybrid cells.

Acetylcholine↗
PubMed1978

Regulation of acetylcholine release from neuroblastoma x glioma hybrid cells.

Neuroblastoma x glioma NG108-15 hybrid cells exposed to N6, O2'-dibutyryladenosine 3':5'-cyclic monophosphate for several days release [3H]acetylcholine in response to serotonin, prostaglandin F2alpha, KCl, or veratridine. NG108-15 cells grown in the absence of dibutyrul cyclic AMP do not respond to an excitatory stimulus by releasing [3H]acetylcholine but can be shifted to a responsive state by treatment with dibutyryl cyclic AMP. Thus, the reactions that are required for acetylcholine release can be regulated in NG108-15 cells, thereby regulating the ability of cells to form synapses and the efficiency of synaptic communication.

Acetylcholine↗
PubMed1978

Regulation of adenylate cyclase activity mediated by muscarinic acetylcholine receptors.

Carbachol, an activator of muscarinic acetylcholine receptors of NG108-15 hybrid cells, inhibits adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] rapidly and reversibly and slowly evokes a 200-300% increase in adenylate cyclase activity over a period of 24-30 hr. Both the inhibition of adenylate cyclase and the gradual increase in enzyme activity are dependent on muscarinic acetylcholine receptors and the receptor activator. Withdrawal of carbachol results in a gradual return of adenylate cyclase activity to control levels over a period of 6 hr; the half-life for decay of enzyme activity is 1.6 hr. These results show that muscarinic acetylcholine receptors mediate both transient and long-lived effects on adenylate cyclase activity that resemble those of opiates.

Adenylyl Cyclases↗
PubMed1978

Synapse turnover: a mechanism for acquiring synaptic specificity.

Neurons are generated in chick retina that are able to form synapses with striated muscle cells for only a brief period during embryonic development. The ability to form synapses is lost with a half-life of 21 hr. Retina neuron-myotube synapses form rapidly but soon are terminated. Chick embryo spinal cord neurons also form synapses with muscle cells for only a limited time during development, but these synapses are long lived. These results show that different classes of synapses turn over at different rates and suggest that part of the specificity of synaptic circuits may be acquired during development by a process of selection based on synapse termination rates.

Age Factors↗
PubMed1978

Studies on synapse formation and opiate dependence.

Neuroblastoma x glioma in NG108-15 cells possess opiate, alpha-adrenergic, and muscarinic acetylcholine receptors, which mediate an inhibition of adenylate cyclase. Growth of cells for 12--48 hours in the presence of a receptor--activator gradually results in a compensatory increase in adenylate cyclase activity. Withdrawal of the receptor ligand then results in relatively long-lived increases in adenylate cyclase activity and intracellular cAMP levels. Thus cells grown in the presence of morphine, norepinephrine, or acetylcholine seem to become dependent on the compound to maintain normal cAMP levels.

Adenylyl Cyclases↗
PubMed1977

Synapse formation between two clonal cell lines.

Clonal neuroblastoma x glioma hybrid cells frequently formed synapses with clonal mouse striated muscle cells. Clonal myotubes were similar to cultured mouse embryo myotubes with respect to acetylcholine sensitivity and other membrane properties examined. However, acetylcholine sensitivity measurements indicate that acetylcholine receptors of clonal myotubes are distributed more uniformly over the cell surface than the receptors of cultured mouse embryo myotubes.

Acetylcholine↗
PubMed1977

Synapse turnover: the formation and termination of transient synapses.

Neurons dissociated from chick embryo retina form synapses with cultured rat striated muscle cells in 35-90 min when neurite extension is uncoupled from later steps in synapse formation. The results suggest that a reaction is required for synapse formation after neurons adhere to muscle cells. All synapses between retina neurons and muscle cells are terminated in 3-10 days depending on the developmental age of the neurons. The half-lives of synapses between muscle cells and retina neurons from 8-, 12-, or 13-day embryos are 36, 26, and 5 hr and mean synapse life-times are 53, 37, and 7.1 hr, respectively. The results show that synapses turn over and that the rate of turnover increases during development. The results suggest that both synapse formation and termination rates are regulated and that the specificity of synaptic connections can be increased by selective termination of synapses.

Animals↗
PubMed1977

Muscarinic acetylcholine receptors of the developing retina.

Six- and 13-day chicken embryo retinas contain 10 and 320 fmol per mg of protein of specific binding sites for 3-[3H]quinuclidinyl benzilate, a ligand of muscarinic acetylcholine receptors. Most of the receptors of 13-day embryo retina were found, by autoradiography, to be localized in two sharp bands within the inner synaptic layer of the retina. In the adult, the receptors were found almost exclusively in three bands in the inner synaptic layer of the retina. A possible mechanism for generating sets of stratified or columnar neurons and relating one set to another is proposed.

Aging↗
PubMed1977

Synthesis of opiate peptides by a clonal pituitary tumor cell line.

Clonal mouse pituitary tumor cells, AtT-20, synthesize at least four species of peptides with opiate activity. The endorphin concentration of AtT-20 cells was estimated to be 300-600 pmol/mg of protein. The two most abundant endorphins with apparent molecular weights of 1800 and 2400 were purified 300- and 24-fold, respectively; additional minor components were found with apparent molecular weights of greater than 3000 and less than 750.

Adenylyl Cyclases↗
PubMed1977

Opiate-dependent modulation of adenylate cyclase.

Reactions mediated by the opiate receptors that inhibit adenylate cyclase (EC 4.6.1.1) are closely coupled to subsequent reactions that gradually increase adenylate cyclase activity of neuroblastoma X glioma NG108-15 hybrid cells. Opiate-treated cells have higher basal-, prostaglandin E1-, and 2-chloroadenosine-stimulated activities than do control cells. However, NaF or guanosine 5'-(beta, gamma-imido)triphosphate abolishes most of the differences in adenylate cyclase activity observed with homogenates from control and opiate-treated cells. Cycloheximide blocked some, but not all, of the opiate-dependent increase in adenylate cyclase activity. These results suggest that the opiate-dependent increase in adenylate cyclase is due to conversion of adenylate cyclase to a form with altered activity. Protein synthesis also is required for part of the opiate effect. We propose that activity of adenylate cyclase determines the rate of conversion of the enzyme from one form to the other and that opiates, by inhibiting adenylate cyclase, alter the relative abundance of low- and high-activity forms of the enzyme.

Adenosine↗
PubMed1976

Synapse formation between clonal neuroblastoma X glioma hybrid cells and striated muscle cells.

Clonal neuroblastoma X glioma hybrid cells were shown to form synapses with cultured, striated muscle cells. The properties of the synapses between hybrid and muscle cells were similar to those of the normal, neuromuscular synapse at an early stage of development. The number of synapses formed and the efficiency of transmission across synapses were found to be regulated, apparently independently, by components in the culture medium. Under appropriate conditions synapses were found with 20% of the hybrid-muscle cell pairs examined; thus, the hybrid cells form synapses with relatively high frequency.

Action Potentials↗
PubMed1976

On the specificity of synapse formation.

Clonal neuroblastome X glioma hybrid cells form synapses with striated muscle cells from different muscles and from different organisms, such as chick, mouse, and rat. Under appropriate conditions 65-80% of the muscle cells exhibited synaptic responses. The results indicate that most striated muscle cells have the same specificity for synapse formation and suggest that synaptogenesis is not dependent on interactions between complementary molecules on neuron and muscle cells that code for different synaptic connections.

Action Potentials↗
PubMed1976

Localization of acetylcholine receptors during synaptogenesis in retina.

Nicotinic acetylcholine receptors are synthesized in chick embryo retina before synapses appear. Most of the receptors are found associated with neurites in the inner synaptic layer of the retina; later in development the receptors appear in the outer synaptic layer. Cells dissociated from retina and cultured in vitro form aggregates and also sort out into regions comprised either of neurites or cell bodies. Most of the nicotinic acetylcholine receptors of aggregates are found associated with neurite regions. The receptor distribution of cultured retina cells thus resembles that of intact retina.

Age Factors↗