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A R Adolph

Publications and source records attributed to A R Adolph.

28 records · Page 2Linked to original sources

Acetylcholine and substance P: action via distinct receptors on carp retinal ganglion cells.

Substance P (SP), a neuropeptide, has been found in amacrine cells in a variety of vertebrate retinas. SP excited many of the ganglion cells we sampled in carp retina; many of these ganglion cells are directly excited by cholinergic agonists. It has been reported that SP modulates cholinergic synaptic transmission in some other neuronal systems by inhibiting or desensitizing cholinergic receptors. SP does not act in this way on the ganglion cell cholinergic receptors in isolated carp retina. Pulses of acetylcholine (ACh), applied to sensitive ganglion cells by microiontophoresis, were set to elicit consistent cellular responses. Application of SP to the retina through a nebulizing system (final concentration about 10(-6) M) did not reduce the excitation produced by the ACh pulse. In earlier work, we showed that the cholinergic receptors were nicotinic; in the present study, SP occasionally excited cells after the retina was treated with a nicotinic cholinergic antagonist, gallamine triethiodide. SP appears to excite cholinergic-sensitive ganglion cells at a postsynaptic site other than their nicotinic cholinergic receptor and via a pathway that does not require a presynaptic, SP-sensitive, ACh-releasing interneuron.

Acetylcholine↗

Specificity of serotoninergic inhibition in Limulus lateral eye.

The receptor specificity for synaptically mediated lateral inhibition in Limulus lateral eye retina was studied by structure-activity correlations of the action of the putative indoleaminergic neurotransmitter, serotonin (5-HT), and its isomers and structural analogs, tryptamine (TRYP), 6-hydroxytryptamine (6HT), 5,6-dihydroxytryptamine (5,6-DHT), 5-hydroxydimethyltryptamine (5-HDMT), and 5-hydroxytryptophan (5-HTP). The 5-HT blockers, lysergic acid diethylamide (LSD), bromo-LSD (BOL), and cinanserin, were also tested. The inhibitory action of the indoleaminergic agonists is highly structure-specific. An hydroxyl group in the 5 position of the indole nucleus, sterically unencumbered by hydroxyls in neighboing positions, is essential. In order of decreasing potency, 5-HT, 5-HDMT, and 5-HTP are active agonists; TRYP, 6-HT, and 5,6-DHT are inactive. Configuration and mobility of the side chains of the active agonists also affect the interaction, and these side-chain characteristics correlate with agonist potency. The receptors for inhibitory action and for transmembranal transport in reuptake are different. Both active agonists and inactive analogs appear to be taken up (Adolph and Ehinger, 1975. Cell Tissue Res. 163:1-14). LSD and BOL have bimodal actions: direct inhibition and agonist blockade. These actions may be mediated via low-specificity presynaptic uptake receptor sites rather than highly specific, postsynaptic, agonist receptor sites.

5-Hydroxytryptophan↗

Putative synaptic mechanisms of inhibition in Limulus lateral eye.

Serotonin (5-HT) perfusion of a thin section of Limulus lateral eye hyperpolarizes retinular and eccentric cell membrane potential, and blocks spike action potentials fired by the eccenteric cell. The indoleamine does not directly affect retinular cell receptor potential or eccenteric cell generator potential in response to light stimuli. LSD perfusion blocks both this inhibitory action of 5-HT and light-evoked, synaptically mediated, lateral inhibition. Iontophoretic application of 5-HT to the synaptic neuropil produces shorter latency and duration and larger amplitude of inhibition than does the perfusion technique. This inhibition is dose dependent; the accompanying inhibitory postsynaptic potential (IPSP) appears to have an equilibrium potential more hyperpolarized than normal resting potential levels of ca. -50 mV. IPSP amplitude is sensitive to extracellular potassium ion concentration: it increases with decreased [K+]0 and decreases with increased [K+]0. LSD blocks the inhibition produced by iontophoretic application of 5-HT. Interaction between light-evoked, natural synaptic transmitter-mediated IPSP's and 5-HT IPSP's suggests a common postsynaptic receptor or transmitter-receptor-permeability change mechanism.

Action Potentials↗

Thermal sensitivity of lateral inhibition in Limulus eye.

The effectiveness of lateral inhibition, measured as spike response decrement in a test ommatidium, produced by activity in a group of neighboring ommatidia, decreases as temperature decreases (Q(10) of 2.6). The corresponding sensory transducer-spike encoding processes have a weaker temperature dependence (Q(10) of 1.6). Relative synaptic delay, the time difference between the latency of inhibition onset and the latency of test receptor excitation, has a strong temperature dependence (Q(10) of 5), while receptor potential onset latency (Q(10) of 1.4) and optic nerve spike conduction velocity (Q(10) of 1.7), two factors inherent in relative synaptic delay, are less temperature sensitive. Oscillations of optic nerve spike response ("bursting") may be produced by thermal adjustment of temperature-sensitive parameters of the lateral inhibitory network in the retina. Burst interval has a strong temperature dependence (Q(10) of 2.4) and broad interspike interval distribution compared to the thermal sensitivity (Q(10) of 1.4) and narrow spike interval spectrum of the response of a single unit within the bursting group.

Action Potentials↗

Serotonin and inhibition in Limulus lateral eye.

The response to light of one ommatidium is reduced or suppressed by simultaneous illumination of neighboring ommatidia. The mechanism of this lateral inhibition may be chemical synaptic transmission, based on the physiological findings of a number of investigators and on the following evidence. The fine structure of the neuropil of the lateral plexus exhibits numerous clear vesicles (ca. 400 A), dense-core vesicles (ca. 700-1400 A), Golgi regions, and other morphological features of neurochemical synapses. The indolealkylamine, serotonin (5-HT), even in nanomolar concentrations, has a potent inhibitory action. An initial, potent inhibitory dose of 5-HT produces a long lasting densensitization to subsequent doses. The desensitization affects lateral inhibition evoked by light stimulation of neighboring receptors, i.e. crossed-desensitization. Eye tissue extracts contain 5-HT and melatonin (MLT) at a level greater than 1 microg/g wet tissue and perhaps as high as 20-30 microg/g, as determined by two-dimensional thin-layer chromatography (TLC) and o-phthaldialdehyde fluorescence assay techniques. Subcellular fractionation on sucrose gradient indicates a peak in 5-HT and MLT content associated with an intermediate density fraction. 5-HT may be an inhibitory transmitter for lateral inhibition. One pathway for metabolism of 5-HT in the lateral eye may be via N-acetylserotonin and melatonin.

Animals↗

Thermal and spectral sensitivities of discrete slow potentials in Limulus eye.

The discrete, subthreshold, slow potential fluctuations (SPF's) which can be recorded intracellularly in Limulus ommatidia are sensitive to temperature and light wavelength. SPF frequency increases with increasing temperature (Q(10) about 3.5) and light intensity. The effects are additive. SPF rise and decay time decrease with increasing temperature (Q(10) between 2 and 3). There is a peak, near 520 nm, in the spectral sensitivity of SPF frequency. This peak may correspond to the wavelength of maximum absorption by rhodopsin in the ommatidia. Hydroxylamine produces a rapid, irreversible reduction of SPF frequency and amplitude perhaps owing to its action on the photopigment. The cornea and crystalline cones fluoresce (peak about 445 nm) when excited by near-ultraviolet energy (380 nm peak) and this fluorescence may influence SPF spectral sensitivity measurements. These findings suggest that the SPF's are the results of photolytic and thermolytic reactions occurring in the ommatidial visual pigments and that they have a role in the mechanisms which transduce light to electrical activity in the visual receptors.

Cell Membrane Permeability↗

Function and structure in retinal transplants.

Embryonic mammalian donor retina transplanted into the subretinal space of a mature host develops into a graft with well-organized, but atypical retinal structure. We tested the effect of this organization on rabbit-to-rabbit graft functional properties, isolating the graft to avoid contamination of graft responses by host retinal activity. Transient ON or ON-OFF spike-like responses and local electroretinograms (L-ERGs) were recorded simultaneously via a single electrode on the graft surface. These response components depended on stimulus diameter, sometimes in a way indicating antagonistic center-surround receptive field organization and spatial tuning (43%). Other times, the responses were an increasing function of stimulus diameter which saturated for large spots (57%). Response amplitudes were a monotonically-increasing function of light intensity over the narrow range tested. The L-ERGs were reminiscent of the proximal negative response or M-wave seen in normal retinas, which reflect light-induced amacrine cell activity. Thus, for the first time, we have shown that these subretinal grafts possess light-transduction and complex functional properties like those in normal retinas. They also possess the cellular complement and synaptic microcircuitry needed to form these physiological properties, Therefore, these results demonstrate a functional ability and capacity in transplants that is required if nerve cell transplantation surgery is to be done with therapeutic aims.

Action Potentials↗

Ultrastructural circuitry in retinal cell transplants to rat retina.

The development of five transplants of fetal retinal tissue to adult rat eyes was examined with the electron microscope. The transplants were of 9 to 10 weeks total age after conception in four cases and 20 weeks in one case. They were at stage E15 when transplanted. Transplants developed in both the epiretinal and subretinal spaces. The transplants were heterogeneously developed with some parts showing almost normal differentiation and others little. Subretinal transplants examined in this study were more developed than epiretinal grafts. Photoreceptor cells developed both inner and outer segments. Their synaptic terminals possessed output ribbon synapses with postsynaptic processes similar to those seen in normal retinas. In regions corresponding to the inner plexiform layer, the adult complement of synapses was seen, including advanced features such as serial synapses as well as reciprocal synapses at bipolar cell dyads. Incompletely differentiated synapses of both the amacrine and bipolar cell types were often observed, especially in the rat epiretinal transplants. Ganglion cell processes could not be identified with certainty. Although transplant cells were adjacent to host photoreceptor cells and pigment epithelium, obvious specializations or interactions were not observed. The experiments suggest that embryonic rat retinal cell transplants develop most or perhaps all of the structural components and neuronal circuitry necessary to transduce light and process some visual information.

Animals↗