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Biomedical subjects

D C Rogers

Publications and source records attributed to D C Rogers.

At least 55 records · Page 3Linked to original sources
PubMed1984

Activation of luteinizing hormone release from pituitary cells by polycations.

In the present work we examined the effect of cationic polymers on the pituitary gonadotrope. Such polymers are widely used to anchor gonadotropes and other cell types to culture dishes and other substrata to which they are not normally adherent. Homopolymers of Lys (eight size classes from 4,000-700,000 daltons) stimulate Ca+2-dependent LH release from pituitary cell cultures. In contrast, release does not occur in response to the epsilon-CBZ or succinyl derivatives (which have no internal charge) or in response to polymers of L-Glu, D-Glu, or Gly. The observation that polymers of D-Lys, L-Lys, and L-Arg all stimulate LH release with similar efficacy and potency indicates that simple charge interactions, rather than interaction with specific polymer-binding sites, are the cause of LH release. Since monomeric Lys neither stimulates LH release nor competitively inhibits release in response to Lys polymers, it appears that multiple charge coordination by Lys polymers is responsible for activation of the release mechanism. Putrescine, spermine, and spermidine (which have more closely spaced charges) do not stimulate LH release, suggesting that a certain minimal distance of charge separation must occur to obtain efficacy. The reduced potency of heteropolymers of Lys (spaced with Ala or Tyr) suggests that a maximal effective distance also exists. Consecutive and concomitant incubation studies indicate that LH released in response to poly-L-Lys or GnRH comes from the same pool as that released by GnRH. The time courses of release are similar for the two compounds.

Animals↗
PubMed1984

Biphasic regulation of the gonadotropin-releasing hormone receptor by receptor microaggregation and intracellular Ca2+ levels.

In the present work we show that Ca2+ is both necessary and sufficient to evoke homologous up-regulation of the gonadotropin-releasing hormone (GnRH) receptor. Extracellular Ca2+ as well as RNA and protein synthesis were required for this event, and it was blocked by Ca2+ ion channel blockers. Drugs which stimulated increased intracellular Ca2+ levels also stimulated receptor up-regulation and enhanced responsiveness even in the absence of added GnRH. Such drugs were effective below the concentrations needed to evoke luteinizing hormone (LH) release, suggesting that enhanced levels of Ca2+ ion, rather than LH depletion, is the responsible agent. A GnRH antagonist did not evoke up- or down-regulation; however, a conjugate of this antagonist, which stimulated microaggregation of the GnRH receptor, also stimulated these biphasic actions. In contrast to up-regulation, down-regulation of the GnRH receptor appears to be Ca2+-independent and does not require RNA or protein synthesis. These data are consistent with a model in which microaggregation of the GnRH receptor is the final step in common to a branched pathway consisting of Ca2+-dependent (LH release, enhanced sensitivity, up-regulation) and Ca2+-independent (desensitization, down-regulation) events.

Animals↗
PubMed1983

Structure-function relationship of calcium ion channel antagonists at the pituitary gonadotrope.

We have compared the potencies of chemically heterogeneous classes of Ca2+ ion channel inhibitors as antagonists of GnRH-stimulated LH release from the rat pituitary. Verapamil and its more potent derivative methoxyverapamil (D600) are effective inhibitors. The 1,4-dihydropyridines, however, had no antagonistic efficacy, and diltiazem had slight inhibitory action, but only when preincubated with cells before GnRH addition. The observation that the potency series of antagonists was identical (verapanoids greater than diltiazem greater than 1,4-dihydropyridines) whether GnRH or veratridine was used to stimulate the release mechanism is consistent with the premise that the same Ca2+ channel is regulated by the receptor and by agents that evoke gonadotropin release by cell depolarization. This potency series is virtually opposite that observed for muscle tissue. Accordingly, these data suggest that the receptor-regulated Ca2+ ion channel of the pituitary gonadotrope is distinct from that described in muscle.

Animals↗
PubMed1982

Is the binocular rivalry mechanism tritanopic?

Binocular rivalry for a series of colored targets was measured in three trichomats and two red-green dichromats by cumulating those times when ony one target or the other was perceived (exclusive visibility time). Targets were black and colored 3 c/deg square-wave gratings, 1 degree in diameter. For trichromats, exclusive visibility time increased as a function of color difference between the targets, but for dichromats there was no effect of color on binocular rivalry. Taken together, these data indicate that the binocular rivalry mechanism is tritanopic: it is responsive to color signals only from the medium- and long-wave-sensitive cones.

Color↗
PubMed1982

Potency enhancement of a GnRH agonist: GnRH-receptor microaggregation stimulates gonadotropin release.

Binding of gonadotropin releasing hormone (GnRH, pyro-Glu1-His2-Trp3-Ser4-Tyr5-Gly6-Leu7-Arg8-Pro9-Gly-NH210) to its plasma membrane receptor is the first step leading to pituitary luteinizing hormone (LH) release. In the present study, we have prepared the ethylene glycol bis(succinimidyl succinate) (EGS) dimer of a GnRH agonist, D-Lys6-GnRH; that is, (D-Lys6-GnRH)-EGS-(D-Lys6-GnRH). The bridge length of the EGS is about 15A. This dimer stimulates LH release from pituitary cultures with full efficacy but slightly less potency than D-Lys6-GnRH indicating that the dimerization merely restricts the action of each molecule of D-Lys6-GnRH with respect to the other. When a concentration of the dimer, which alone is too low to evoke substantial LH release, is incubated with pituitary cell cultures in the presence of antibody (AB) against D-Lys6-GnRH, considerable potency enhancement occurs. LH release in response to the AB-dimer conjugate requires extracellular Ca2+ and is blocked by Pimozide. The monovalent form (i.e. reduced pepsin fragment) of AB is ineffective in stimulating release. The addition of antibody to the dimer appears to confer the ability to cross-link receptors and indicates that receptor microaggregation as such is sufficient to activate the effector system in these cells and evoke release.

Animals↗
PubMed1982

Newer laboratory approaches for assessing visual dysfunction.

The crucial point that will be emphasized throughout this report is the potential utility of analyzing visual cortical receptive field (RF) properties of the single-cell level as a sensitive and reliable neurotoxicity screening tool. Numerous studies employing exposure of kittens to altered visual environments during the critical period have demonstrated that particular classes of RFs can be selectively affected while sparing others. There has been a rapid proliferation of new methods used to investigate such effects. An important current trend involves the development of multidisciplinary combinations of approaches. The various maneuvers reviewed here seem adaptable to studying neurotoxic insult of the sensitive properties of cortical visual neurons, particularly in the cat or monkey. Conceivably, a general disruption of cortical RF properties might be expected following toxic exposure since individual RF properties are generally not determined by completely independent mechanisms. In fact, some toxicants might produce a general degradation of RF properties akin to the electrophysiological results reported for long-term dark rearing or binocular deprivation.

Animals↗
PubMed1982

Visual development: early experience with torsionally disparate images.

Environmental influences on the developing primary visual cortex of kittens were studied by exposing dark reared kittens to prism-induced interocular rotational disparities of 32 degrees, the visual input rotated equally and oppositely in the two eyes. The present report describes preliminary results obtained from two kittens that received this altered visual exposure during 1-6 hours each day from 4 until 12 weeks of age. Subsequent single-unit recordings from the striate cortex revealed three major changes in functional cortical visual physiology. First, there was a disruption in binocularity, with many more cells being monocularly driven in the rotated conditions compared to control conditions. Second, there was an increased variance in the distribution of cells' interocular differences in preferred stimulus orientation (interocular orientation disparity, or IOD) as compared to control conditions. Third, changes were noted in orientation tuning and in the distribution of orientation preferences: cells most selective for orientation tended to be in the extreme ocular dominance groups, and monocular cells were often the most highly selective; also, both binocular and monocular cells showed a tendency for preferred orientations for both eyes to fall near the horizontal or vertical (+/- 22.5 degrees). Thus, a large optically-induced orientation disparity between the two eyes' visual fields during the critical period can modify the characteristics of striate cortical neurons, particularly binocularity and IOD. In addition, these results indicate that an inherent cortical mechanism may ensure the encoding of horizontal and vertical orientation specificities for a subclass of primary visual cortical neurons.

Aging↗
PubMed1981

Stimulation of pituitary gonadotropin release does not require internalization of gonadotropin-releasing hormone.

Binding of gonadotropin-releasing hormone (GnRH, pyro-Glu1-His2-Trp3-Ser4-Tyr5-Gly6-Leu7-Arg8-Pro9-Gly-NH210) to its plasma membrane receptor is the first step leading to the release of pituitary luteinizing hormone. As in the case of other plasma membrane receptors, patching, capping, and internalization of this hormone-receptor complex occurs rapidly following exposure of cultured pituitary cells to physiological levels of releasing hormone. In the present study we sought to determine whether gonadotropin release could occur under conditions which rigorously excluded internalization. A GnRH analog, D-Lys6-GnRH (to which a small quantity of [125I]iodoTyr5-D-Lys6-GnRH was added), was coupled by its epsilon-amino group with an N-hydroxysuccinimide ester then, through a 10-A spacer arm, to a cross-linked agarose matrix. Exposure of the product to proteases, soaps, detergents, solvents, chaotropic agents, or cell cultures resulted in dissociation of < 0.28% of biologically active releasing hormone. The apparent potency of the immobilized analog was one-fourth that of the free form and it was still capable of evoking a full luteinizing hormone secretory response. It can, therefore, be concluded that internalization of GnRH is not required for gonadotropin release.

Animals↗
PubMed1981

Immunofluorescent and structural features of cells in the intervascular stroma of the amphibian carotid labyrinth.

The amphibian carotid labyrinth consists of a pars cavernosa, the main chamber of which is in communication with both the base of the external carotid artery, and the vessels of the labyrinthine pars capillaris. On the walls of the main chamber is a network of thick strands of connective tissue and modified smooth muscle cells surrounding the openings into the p. capillaris. These openings lead into wide-diameter atrial vessels, which in turn branch to form the short narrow-diameter vessels. The short vessels form the major component of the labyrinth. A few extremely narrow-diameter vessels are also present. The short vessels open into the roots of the internal carotid artery on the ventral aspect of the carotid labyrinth. The intervascular stroma of the p. capillaris contains numerous stellate and bipolar cells. These cells give a positive response to an immunofluorescent technique specific for smooth muscle myosin and tropomyosin. As the ultrastructural features of these cells are comparable in many respects to smooth muscle, they have been designated as modified smooth muscle cells. It is proposed that these cells act in both an active and passive fashion in maintaining the luminal dimensions of the short vessels relatively constant.

Animals↗
PubMed1981

Inhibition of gonadotropin-releasing hormone-stimulated luteinizing hormone release by pimozide: evidence for a site of action after calcium mobilization.

In the present work, we show that pimozide is a noncompetitive antagonist of gonadotropin-releasing hormone (GnRH)-stimulated LH release from pituitary cell cultures. For several other neurotropic agents, the concentration needed to inhibit 50% of LH release in response to GnRH correlates well with the ability to inhibit enzyme activation by calmodulin in vitro. Pimozide does not alter the affinity or amount of releasing hormone binding by the GnRH receptor. The additional observation that pimozide inhibits Ca2+ ionophore (A23187 and ionomycin)-stimulated LH release suggests that the locus of pimozide action is after Ca2+ mobilization. Pimozide is known to bind and inactivate the Ca2+-calmodulin complex, and as Ca2+ is a second messenger for GnRH, it is possible that calmodulin is the target of pimozide in this system.

Animals↗
PubMed1980

The ultrastructural characteristics of the apical cell in the neuroepithelial bodies of the toad lung (Bufo marinus).

The cytological features and membrane specialisations of neuroepithelial cells (apical cells) in direct contact with the lumen of the lung were studied with transmission and scanning electron microscopy. The luminal surface of the apical cell is characterised by microvilli, a cilium with an 8 + 1 microtubular pattern and numerous coated vesicles. The cytoplasmic region immediately beneath the luminal plasma membrane contains numerous smooth-walled vesicles, tubules and microtubules, a few microfilaments and dense granules (15-20 nm in diameter). The luminal pole of the cell is marked off from the basal or vascular pole by a well-defined terminal web associated with junctional complexes. Protrusion of the luminal pole occurs as a transient phenomenon and is accompanied by a pinching in of the cell at the terminal web. It is proposed that the distinctive features of the luminal pole of the apical cell are comparable to those of recognised chemoreceptor cells. It is also proposed that in view of the common features of apical and basal cells the apical cell functions as a receptor/transducer and the basal cells served as an accessory source of peptides/5-hydroxytryptamine to be released on stimulation of the apical cell. Furthermore, we have drawn attention to the structural heterogeneity of the neuroepithelial bodies in various vertebrate classes.

Animals↗
PubMed1980

Qualitative change in gonadotropin during normal aging in the male rat.

In the present work we have compared a pituitary LH extract and circulating LH from adult male rats (5 months old) with those from rats 10, 13, or 24 months old. The pituitary and circulating forms of LH prepared from old animals had a higher apparent molecular weight, judged by gel filtration, than LH preparations from younger animals. This difference may be due to increased sialic acid content of the larger form, since simultaneous neuraminidase treatment of this gonadotropin preparation and our internal reference standard ([125I]LH prepared from a normal adult rat) abolished the apparent size difference. In addition, the larger form prepared from old rats was cleared more slowly from the circulation of immature females than the form prepared from young rats. The apparent increase in sialation during normal aging could be mimicked in young animals which were castrated. Injections of testosterone propionate reversed the effect in both castrates and old animals. The data suggest that the diminished levels of metabolically active testosterone or other steroid metabolites in old male rats may result in qualitative alterations in the stored and released forms of LH.

Aging↗
PubMed1980

Gonadotropin release from pituitary cultures following activation of endogenous ion channels.

In primary rat pituitary cell cultures, activation of Na+ channels resulted in Na+ and Ca2+ dependent gonadotropin release. This occurred with the same efficacy and over the same time course as that stimulated by gonadotropin releasing hormone (GnRH). In contrast, GnRH required extracellular Ca2+, but not Na+ for its action. These results indicate that the gonadotrope has ion channels which resemble those found in neural tissues.

Aconitine↗
PubMed1978

Innervation and cytochemistry of the neuroepithelial bodies in the ciliated epithelium of the toad lung (Bufo marinus).

Neuroepithelial bodies (NEB) were identified in the lung of Bufo marinus. The characteristics of the cells and their innervation were studied with electron and fluorescence microscopy before and after close vagosympathetic denervation. The bodies consist of low columnar cells which rest on the epithelial basal lamina. The majority of the cells do not reach the lumen of the lung (basal cells); the few which do (apical cells) are bordered by microvilli and possess a single cilium. The neuroepithelial cell cytoplasm contains a variety of organelles the most characteristic of which are dense cored vesicles. Microspectrofluorometry and electron microscopic cytochemistry indicate significant quantities of 5-hydroxytryptamine in these cells. The neuroepithelial bodies could be divided into three groups on the basis of their innervation: 1) About 60% of the NEBs are innervated solely by nerve fibers containing agranular vesicles which form reciprocal synapses; 2) about 20% are innervated solely by adrenergic nerve fibres which from distinct synaptic contacts; and 3) the remaining 20% are innervated by both types of nerve fibres. It is proposed that the NEBs are receptors monitoring intrapulmonary P CO2 and so leading to modulation of activity in afferent nerve fibres (type containing a granular vesicles). The presence of NEBs soley with an adrenergic (efferent) innervation poses a problem with this interpretation.

Amines↗