scholarly journals Hormonal control of transmitter plasticity in insect peptidergic neurons. II. Steroid control of the up-regulation of bursicon expression

1993 ◽  
Vol 181 (1) ◽  
pp. 195-212 ◽  
Author(s):  
N. J. Tublitz ◽  
P. K. Loi

Each abdominal ganglion of the central nervous system of the tobacco hawkmoth, Manduca sexta contains four individually identified lateral neurosecretory cells (LNCs) that undergo a postembryonic transmitter switch in vivo. In the embryonic and caterpillar stages, the primary LNC transmitter is cardioacceleratory peptide 2 (CAP2), a myoregulatory peptide. During metamorphosis, these cells stop expressing CAP2 and instead produce bursicon, a classic insect peptide hormone responsible for cuticular tanning. We have previously reported that this transmitter plasticity is under the control of the insect steroid hormone 20-hydroxyecdysone (20-HE), which surges twice during the last larval instar. In that report we showed that the CAP2 decline is indirectly regulated by the first 20-HE rise, the commitment pulse (CP). Here we provide evidence that the rise in bursicon levels in the LNCs is directly triggered by the second 20-HE surge, the prepupal peak (PP). We performed several experimental manipulations that exposed LNCs to the PP without the CP; cells treated in this manner exhibited a significant rise in bursicon content. In contrast, bursicon levels remained unchanged in those LNCs exposed only to the CP. Exposure to the PP triggered a precocious increase in bursicon expression in LNCs from the penultimate larval stage. Increased bursicon levels in the LNCs were also induced by direct infusion of 20-HE. Taken together, the results of these experiments suggest that the rise in bursicon in the LNCs during metamorphosis is due to the direct action of the PP on the LNCs. Thus, the two 20-HE surges combine to regulate the CAP2-to-bursicon switch in the LNCs, the first acting indirectly to cause a decline in CAP2 levels and the second triggering a rise in bursicon expression, possibly by a direct action on the LNCs.

1993 ◽  
Vol 181 (1) ◽  
pp. 175-194 ◽  
Author(s):  
P. K. Loi ◽  
N. J. Tublitz

Transmitter plasticity, the ability to alter transmitter expression, has been documented in several different preparations both in vivo and in vitro. One of these is the tobacco hawkmoth, Manduca sexta, whose central nervous system contains four individually identified lateral neurosecretory cells (LNCs) that undergo a postembryonic transmitter switch in vivo. In larvae, the LNCs express high levels of a myoregulatory peptide, cardioacceleratory peptide 2 (CAP2). In contrast, the predominant LNC transmitter in adult moths in bursicon, a classic insect peptide hormone responsible for cuticular tanning. Here we show that the CAP2-to-bursicon conversion by the LNCs is a multi-step process beginning with a decline in CAP2 levels midway through the final larval stage. We provide several lines of evidence that this CAP2 drop is regulated by the insect steroid hormone 20-hydroxyecdysone (20-HE). The LNCs exhibit a fall in CAP2 levels at the beginning of metamorphosis, immediately after the commitment pulse of 20-HE when steroid levels are elevated. LNCs not exposed to this 20-HE rise do not exhibit a decline in CAP2 level. The transmitter switch can also be prevented by using an analog of juvenile hormone to create a larval hormonal environment during the commitment pulse of 20-HE. The CAP2 decline in the LNCs could be directly induced by exogenous steroid application, but only under conditions where the LNCs remained connected to the brain. Thus, the first step in the transmitter switch by the LNCs, the decline in CAP2 levels, is triggered by the commitment pulse of 20-HE, which may act indirectly through a set of steroid-sensitive cells in the brain.


1999 ◽  
Vol 277 (2) ◽  
pp. F251-F256 ◽  
Author(s):  
Michael Gekle ◽  
Sigrid Mildenberger ◽  
Christoph Sauvant ◽  
Dallas Bednarczyk ◽  
Stephen H. Wright ◽  
...  

The effect of ligands for phospholipase C-coupled receptors and of protein kinase C (PKC) stimulation with phorbol ester [phorbol 12-myristate 13-acetate (PMA)] or 1,2-dioctanoyl- sn-glycerol on the activity of the basolateral organic anion transporter (OAT) in S2 segments of single, nonperfused rabbit proximal tubules (PT) was measured with the use of fluorescein and epifluorescence microscopy. The initial uptake rate (25 s, OAT activity) was measured in real time by using conditions similar to those found in vivo. Stimulation of PKC with PMA or 1,2-dioctanoyl- sn-glycerol led to an inhibition of OAT activity, which could be prevented by 10−7 mol/l of the PKC-specific inhibitor bisindolylmaleimide. The α1-receptor agonist phenylephrine as well as the peptide hormone bradykinin induced a reversible decrease of OAT activity, which was prevented by bisindolylmaleimide. The observed effect was not due to a decrease in the concentration of the counterion α-ketoglutarate or to impaired α-ketoglutarate recycling, because it was unchanged in the continuous presence of α-ketoglutarate or methyl succinate. We conclude that physiological stimuli can inhibit the activity of OAT in rabbit PT via PKC. The effect is not mediated by alterations in counterion availability but by a direct action on the OAT.


1978 ◽  
Vol 234 (2) ◽  
pp. F135-F140
Author(s):  
C. M. Gregg ◽  
R. L. Malvin

It is now thought that angiotensin II can stimulate antidiuretic hormone (ADH) release in vivo by a direct action in the central nervous system but it is not known whether the locus of stimulation is the hypothalamus or the neurohypophysis or both. Isolated rat neural lobes incubated for 10 min in buffer containing angiotensin II (200 ng/ml or 2 microgram/ml) did not increase ADH release compared to control values, but addition of KCl (60 mM) to the bath markedly stimulated ADH release. However, intact hypothalamoneurohypophysial systems (containing the supraoptic nuclei) incubated with angiotensin II (200 ng/ml or 2 microgram/ml) did show a pronounced stimulation of ADH release. The data support the hypothesis that angiotensin II, at least in vitro, has a central effect on ADH release which is at the level of the hypothalamus.


1998 ◽  
Vol 201 (21) ◽  
pp. 2981-2992
Author(s):  
H. W. Mcgraw ◽  
KRS. Prier ◽  
J. C. Wiley ◽  
N. J. Tublitz

The lateral neurosecretory cells (LNCs) in the tobacco hornworm Manduca sexta undergo a switch in neurotransmitter phenotype during pupation. Concurrent with this change in function, the LNCs undergo a major morphological reorganization. This study characterizes the morphological change and its underlying cause. In the larva, the LNC has a very compact dendritic arborization in a small volume of neuropil ipsilateral to the cell soma. In the adult moth, the LNC arborization extends through a much larger volume of neuropil, including the contralateral side of the ganglion. Using both in vivo manipulations and a single-cell culture system, we show that this change in morphology is probably triggered by two pulses of the steroid hormone 20-hydroxyecdysone (20-HE): a small commitment peak and a larger prepupal pulse. These are the same two pulses of 20-HE as those previously shown jointly to cause the change in transmitter phenotype. This work, in conjunction with a previous study on the transmitter switch, documents the orchestration of major morphological and biochemical changes in a set of identified neurons by a single hormone.


1979 ◽  
Vol 42 (4) ◽  
pp. 1185-1197 ◽  
Author(s):  
E. Mayeri ◽  
P. Brownell ◽  
W. D. Branton

1. A survey of identified cells of the abdominal ganglion of Aplysia was undertaken to determine the extent of bag cell influence in the ganglion. Bursts of bag cell spike activity lasting 5--40 min were elicited by brief, 0.6- to 2 s local stimulation while recording simultaneously from bag cells and other ganglion cells with intracellular electrodes. 2. Slow inhibition occurs in giant cell R2, neurosecretory cells R3-R14, and ink-gland motoneurons, L14A, B, C. The cells remain hyperpolarized for from 15 to 60 min. 3. Transient excitation occurs in mechanoreceptor cells L1 and R1. The cells are strongly depolarized by a slow excitatory potential that lasts for about 10 min and produces spike activity for 3--7 min. 4. Prolonged excitation occurs in some cells of the LB and LC identified cell clusters. The cells are depolarized and spike activity is increased for 3 h or more. 5. A biphasic response occasionally occurs in the command interneuron L10. Inhibition of this cell lasts 10--15 min and is followed by excitation for several hours. Excitation is accompanied by facilitation of synaptic potentials for 40--60 min in cells innervated by L10; the facilitation apparently results from the increase in L10 firing rate. 6. The results indicate that the bag cells have multiple types of actions and affect large numbers of ganglion neurons. All effects have the slowly graded onsets and prolonged durations to be expected of hormonally mediated interactions. 7. Previous studies have indicated that in intact animals the bag cell burst discharge initates a stereotyped egg-laying behavioral pattern that persists for several hours (3, 27). The present data support the hypothesis that certain elements of egg-laying behavior and homeostasis are regulated by a direct action of the bag cells on the central nervous system.


Before detailed studies of the physiology and pharmacology of central peptidergic neurons can be undertaken, the location of these neurons must be determined and the mechanism(s) by which they synthesize their peptide products must be explored. In the previous paper, Dr Hökfelt described his elegant immunohistachemical studies, which are designed to answer the questions: Where are peptidergic perikarya?; Where do these perikarya send their processes?; Do these processes branch extensively and innervate several structures?; and Do peptidergic cells contain more than one active product? By studying the effects of lesions on peptide levels in microdissected tissue samples, immunocytochemical data can be confirmed and extended. The microanalytical approach also allows one to determine the nature of the immunologically active substances in a tissue extract, and in vivo or in vitro pulse–chases studies provide the ultimative validation of immunohistological localization of peptidergic perikarya and new information about the biosynthesis of peptides and regulation of this biosynthesis process. Our recent studies of central proopiocoritn- and neurophusin/vasopressin-producing neurons will illustrate the above points.


Endocrinology ◽  
2019 ◽  
Vol 160 (11) ◽  
pp. 2737-2747 ◽  
Author(s):  
Edward S Jones ◽  
Nicolas Nunn ◽  
Adam P Chambers ◽  
Søren Østergaard ◽  
Birgitte S Wulff ◽  
...  

Abstract To study the effects of an analog of the gut-produced hormone peptide YY (PYY3-36), which has increased selectivity for the Y2 receptor; specifically, to record its effects on food intake and on hypothalamic neuropeptide Y/agouti-related peptide (NPY/AgRP) neuron activity. NNC0165-1273, a modified form of the peptide hormone PYY3-36 with potent selectivity at Y2 receptor (>5000-fold over Y1, 1250-fold over Y4, and 650-fold over Y5 receptor), was tested in vivo and in vitro in mouse models. NNC0165-1273 has fivefold lower relative affinity for Y2 compared with PYY3-36, but >250-, 192-, and 400-fold higher selectivity, respectively, for the Y1, Y4, and Y5 receptors. NNC0165-1273 produced a reduction in nighttime feeding at a dose at which PYY3-36 loses efficacy. The normal behavioral satiety sequence observed suggests that NNC0165-1273 is not nauseating and, instead, reduces food intake by producing early satiety. Additionally, NNC0165-1273 blocked ghrelin-induced cFos expression in NPY/AgRP neurons. In vitro electrophysiological recordings showed that, opposite to ghrelin, NNC0165-1273 hyperpolarized NPY/AgRP neurons and reduced action potential frequency. Administration of NNC0165-1273 via subcutaneous osmotic minipump caused a dose-dependent decrease in body weight and fat mass in an obese mouse model. Finally, NNC0165-1273 attenuated the feeding response when NPY/AgRP neurons were activated using ghrelin or more selectively with designer receptors. NNC0165-1273 is nonnauseating and stimulates a satiety response through, at least in part, a direct action on hypothalamic NPY/AgRP neurons. Modification of PYY3-36 to produce compounds with increased affinity to Y2 receptors may be useful as antiobesity therapies in humans.


1958 ◽  
Vol 35 (3) ◽  
pp. 520-551 ◽  
Author(s):  
HOWARD A. SCHNEIDERMAN ◽  
JUDITH HORWITZ

1. Experiments have been conducted to determine the extrinsic factors that cause facultative diapause in two parasitic chalcid wasps, Mormoniella vitripennis and Tritneptis klugii, and to analyse the mechanism of diapause termination. 2. In both species diapause occurs in the last larval instar after the feeding period has ended and just prior to defaecation. The diagnostic feature of the diapausing larva is that it does not immediately moult into a pupa. 3. In Mormoniella exposing females to low temperature during oögenesis causes their progeny to enter diapause at the end of the last larval instar. Low temperature thus causes the female to lay an egg that is qualitatively different from an ordinary egg in that the larva emerging from it eventually enters diapause. This action of low temperature on the female wears off after several days and the wasp returns to producing non-diapausing offspring. 4. In Tritneptis low temperature also produces diapause, but in this species low temperature, to be effective, must act on the larva itself between the second and final instar to produce diapause in that generation. 5. The diapause of Mormoniella was considered in relation to maternally induced diapause in other species and two possible mechanisms for the action of low temperature were suggested, namely, a direct action on the ovaries or an indirect action through the maternal production of a diapause hormone. 6. It was found that exposure to low temperatures enables larvae of both species to break diapause and complete their development when subsequently placed at 25° C. 7. The mechanism of action of low temperature in terminating diapause was examined in Mormoniella by exposing larvae to various temperature régimes in the presence and absence of oxygen. 8. Ten weeks at 5° C. enabled nearly 90% of the larvae to terminate diapause when returned to 25° C.; after 6 weeks at 5° C. less than 10% developed. Chilling at 2° C. was more effective than 5 or 1o° C., while temperatures above 15 or below -6° C. were ineffective. 9. Although diapause was never terminated by keeping larvae continually at temperatures above 15° C., a period of exposure to temperatures above 15° C. prior to chilling decreased the amount of chilling necessary to terminate diapause. 10. Larvae chilled in the absence of oxygen for as long as 28 weeks failed to break diapause but developed when subsequently rechilled in air. 11. After receiving a threshold exposure to low temperature larvae could not be returned to diapause by temperature shocks as high as 45° C.; however, the effects of subthreshold chilling were reversed by exposure to 25° C. Thus, animals chilled for a total of 20 weeks, with 1 week of warming after each week of chilling, failed to develop. Similarly, it was found that interrupting 8 weeks of chilling on the 25th day by 4 days of warming partially undid the chilling. 12. When warming was conducted in the absence of oxygen it failed to undo the effects of subthreshold chilling and the termination of diapause was markedly accelerated. Indeed, when larvae were chilled for a subthreshold period, a brief interval of anaerobic warming sufficed to enable some of the larvae to terminate diapause. 13. In addition to the above, a variety of other experiments were conducted with alternating periods of chilling and warming in the presence and absence of oxygen. These led to a hypothesis which seems to account for the action of low temperature in terminating larval diapause. 14. The hypothesis focuses attention on the neurosecretory cells of the insect's brain and suggests that low temperature slows down an aerobic breakdown reaction within the larval brain and permits the synthesis of a substance necessary for neurosecretory activity. The initial stages of the synthetic reaction are aerobic but later stages are favoured by anaerobic warming. The nature of these reactions was discussed.


1992 ◽  
Vol 165 (1) ◽  
pp. 241-264 ◽  
Author(s):  
N. J. Tublitz ◽  
A. T. Allen ◽  
C. C. Cheung ◽  
K. K. Edwards ◽  
D. P. Kimble ◽  
...  

The functional relationship between cardioacceleratory peptide 2 (CAP2) and hindgut activity during wandering behaviour was investigated in fifth-instar larvae of the tobacco hawkmoth Manduca sexta. Inspection of the alimentary canal on the day prior to wandering showed that the gut, in preparation for metamorphosis, was voided of all contents by 18:00 h. Associated with this event, which we refer to as ‘gut emptying’, was an increase in the frequency of hindgut contractions measured in vivo. No change in heart activity was seen during this developmental period. Measurements of the amount of CAP2 in the central nervous system (CNS) of fifth-instar caterpillars revealed that CAP2 storage levels declined sharply on the day of gut emptying. The drop in CNS levels of CAP2 at gut emptying was temporally correlated with the appearance of CAP2 in the haemolymph. CAP2, when applied at physiological concentrations to an in vitro larval hindgut bioassay, caused changes in several parameters, including contraction frequency and amplitude, and basal tension. In vivo administration of CAP2 elicited hindgut responses that were qualitatively and quantitatively similar to those seen in vitro. Developmental studies on changes in CAP2 responsiveness during the last larval instar demonstrated that the hindgut is maximally sensitive to CAP2 on the day of gut emptying. Direct evidence in support of a role for CAP2 in fifth-instar larvae was provided by experiments in which the increase in gut activity in vivo seen at gut emptying was significantly reduced by injections of an anti-CAP antibody. Based on data from cobalt backfills and anti-CAP immunohistochemical staining, we propose that CAP2 exerts its effect on the larval hindgut at wandering via a local release from CAP-containing neurones in the terminal ganglion that project directly to the hindgut.


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