Titan's interaction with the Saturnian magnetosphere

In this thesis, a combination of data analysis and test particle simulations is used in order to study several aspects of the complex interaction of Titan with the Saturnian magnetosphere. First, the energetic charged particles environment at the orbital distance of Titan is studied using data from the MIMI/LEMMS instrument. Average fluxes and spectral slopes for energetic ions and electrons are analysed. A large variability is found, and it is interpreted as originated from the high mobility of the energetic ions and electrons, making a simple classification of this environment practically impossible, with only a weak correlation between the ion average fluxes with the plasma environment detectable and an asymmetry between the noon-to-dusk and midnight-to-dawn sectors. Second, the effect of local electromagnetic field disturbances in the access of energetic H+ and O+ ions is studied. By studying the trajectories of individual particles to predict where they will deposit their energy, differences in ionisation rates at different locations around the moon of almost 80% are found for H+ ions and of more than 15% for the case of O+ ions. Finally, the contribution of freshly produced pickup ions to the overall mass loss of the atmosphere is investigated by looking at particular signatures left by these ions in the thermal plasma data from the CAPS/IMS instrument. A statistical survey of all the flybys with available data leads to a constraint of the region around the moon where these ions are detected. Mass losses on the anti-Saturn side of the moon of between 570 kg/day and 1 tonne/day are derived depending on the species, accounting for a small fraction of the total losses estimated from distant tail observations

In search of subsurface oceans within the Uranian moons

The Galileo mission to Jupiter discovered magnetic signatures associated with hidden sub-surface oceans at the moons Europa and Callisto using the phenomenon of magnetic induction. These induced magnetic fields originate from electrically conductive layers within the moons and are driven by Jupiter’s strong time-varying magnetic field. The ice giants and their moons are also ideal laboratories for magnetic induction studies. Both Uranus and Neptune have a strongly tilted magnetic axis with respect to their spin axis, creating a dynamic and strongly variable magnetic field environment at the orbits of their major moons. Although Voyager-2 visited the ice giants in the 1980s, it did not pass close enough to any of the moons to detect magnetic induction signatures. However, Voyager-2 revealed that some of these moons exhibit surface features that hint at recent geologically activity, possibly associated with sub-surface oceans. Future missions to the ice giants may therefore be capable of discovering sub-surface oceans, thereby adding to the family of known “ocean worlds” in our solar system. Here, we assess magnetic induction as a technique for investigating sub-surface oceans within the major moons of Uranus. Furthermore, we establish the ability to distinguish induction responses created by different interior characteristics that tie into the induction response: ocean thickness, conductivity, and depth, and ionospheric conductance. The results reported here demonstrate the possibility of single-pass ocean detection and constrained characterization within the moons of Miranda, Ariel, and Umbriel, and provide guidance for magnetometer selection and trajectory design for future missions to Uranus

Survey of pickup ion signatures in the vicinity of Titan using CAPS/IMS

Pickup ion detection at Titan is challenging because ion cyclotron waves are rarely detected in the vicinity of the moon. In this work, signatures left by freshly produced pickup heavy ions (m/q ∼ 16 to m/q ∼ 28) as detected in the plasma data by the Cassini Plasma Spectrometer/Ion Mass Spectrometer (CAPS/IMS) instrument on board Cassini are analyzed. In order to discern whether these correspond to ions of exospheric origin, one of the flybys during which the reported signatures were observed is investigated in detail. For this purpose, ion composition data from time-of-flight measurements and test particle simulations to constrain the ions' origin are used. After being validated, the detection method is applied to all the flybys for which the CAPS/IMS instrument gathered valid data, constraining the region around the moon where the signatures are observed. The results reveal an escape region located in the anti-Saturn direction as expected from the nominal corotation electric field direction. These findings provide new constraints for the area of freshly produced pickup ion escape, giving an approximate escape rate of inline image ions· s−1

A transient enhancement of Mercury's exosphere at extremely high altitudes inferred from pickup ions

Mercury has a global dayside exosphere, with measured densities of 10-2 cm-3 at ~1500 km. Here we report on the inferred enhancement of neutral densities (<102 cm-3) at high altitudes (~5300 km) by the MESSENGER spacecraft. Such high-altitude densities cannot be accounted for by the typical exosphere. This event was observed by the Fast-Imaging Plasma Spectrometer (FIPS), which detected heavy ions of planetary origin that were recently ionized, and "picked up" by the solar wind. We estimate that the neutral density required to produce the observed pickup ion fluxes is similar to typical exospheric densities found at ~700 km altitudes. We suggest that this event was most likely caused by a meteroid impact. Understanding meteoroid impacts is critical to understanding the source processes of the exosphere at Mercury, and the use of plasma spectrometers will be crucial for future observations with the Bepi-Colombo mission

Antidromic vasodilatation and the migraine mechanism

Despite the fact that an unprecedented series of new discoveries in neurochemistry, neuroimaging, genetics and clinical pharmacology accumulated over the last 20 years has significantly increased our current knowledge, the underlying mechanism of the migraine headache remains elusive. The present review article addresses, from early evidence that emerged at the end of the nineteenth century, the role of ‘antidromic vasodilatation’ as part of the more general phenomenon, currently defined as neurogenic inflammation, in the unique type of pain reported by patients suffering from migraine headaches. The present paper describes distinctive orthodromic and antidromic properties of a subset of somatosensory neurons, the vascular- and neurobiology of peptides contained in these neurons, and the clinical–pharmacological data obtained in recent investigations using provocation tests in experimental animals and human beings. Altogether, previous and recent data underscore that antidromic vasodilatation, originating from the activation of peptidergic somatosensory neurons, cannot yet be discarded as a major contributing mechanism of the throbbing head pain and hyperalgesia of migraine

[Nphe(1)]nociceptin-(1-13)NH2 selectively antagonizes nociceptin effects in the rabbit isolated ileum

When suspended in vitro in isolated organ baths, segments of the rabbit ileum show a fairly strong and stable spontaneous activity, which derives from the continuous release of acetylcholine and the activation of muscarinic receptors, since the activity is completely eliminated by atropine. Dynorphin A pEC50: 8.6"0.07., neuropeptide Y and its congener human pancreatic polypeptide pEC50: 9.40"0.10., and nociceptin pEC50: 8.08"0.12. dose-dependently inhibit the spontaneous activity through the activation of receptors, which are specifically antagonised respectively by naloxone p A2: 7.17"0.12., 2-naphtalen-1-ylamino.-3-phenylpropionitrile JCF 104; p A2: 5.80"0.10., and wNphe1xnociceptin-1–13.NH2 p A2: 6.17"0.19.. This last compound, a selective nociceptin-receptor OP4. antagonist, inhibits the effect of nociceptin in a competitive manner, as demonstrated by Schild analysis. wNphe1xnociceptin-1–13.NH2 also antagonizes the effects of other OP4 receptor ligands such as the full agonist, nociceptin-1–13.-NH2, and the partial agonists, wPhe1cCH2–NH.Gly 2 xnociceptin-1–13.-NH2 intrinsic activity a E.s0.5. and Ac-RYYWK-NH2 a Es0.5., with p A2 values ranged from 5.8 to 6.2. These results indicate that the functional site mediating the inhibitory effect of nociceptin in the rabbit ileum, is pharmacologically identical to the OP4 sites of other species mouse, rat, guinea pig, man., since the potencies p A2 values. of the pure and competitive antagonist wNphe1xnociceptin-1–13.NH2 is very similar to the values obtained in the other species. Moreover, the rabbit ileum is one of the few isolated organs that allow classifying compounds, which interact with OP4 receptors as full agonists, partial agonists, or pure antagonists

[Nphe(1)]nociceptin-(1-13)NH2 selectively antagonizes nociceptin effects in the rabbit isolated ileum

When suspended in vitro in isolated organ baths, segments of the rabbit ileum show a fairly strong and stable spontaneous activity, which derives from the continuous release of acetylcholine and the activation of muscarinic receptors, since the activity is completely eliminated by atropine. Dynorphin A pEC50: 8.6"0.07., neuropeptide Y and its congener human pancreatic polypeptide pEC50: 9.40"0.10., and nociceptin pEC50: 8.08"0.12. dose-dependently inhibit the spontaneous activity through the activation of receptors, which are specifically antagonised respectively by naloxone p A2: 7.17"0.12., 2-naphtalen-1-ylamino.-3-phenylpropionitrile JCF 104; p A2: 5.80"0.10., and wNphe1xnociceptin-1\u201313.NH2 p A2: 6.17"0.19.. This last compound, a selective nociceptin-receptor OP4. antagonist, inhibits the effect of nociceptin in a competitive manner, as demonstrated by Schild analysis. wNphe1xnociceptin-1\u201313.NH2 also antagonizes the effects of other OP4 receptor ligands such as the full agonist, nociceptin-1\u201313.-NH2, and the partial agonists, wPhe1cCH2\u2013NH.Gly 2 xnociceptin-1\u201313.-NH2 intrinsic activity a E.s0.5. and Ac-RYYWK-NH2 a Es0.5., with p A2 values ranged from 5.8 to 6.2. These results indicate that the functional site mediating the inhibitory effect of nociceptin in the rabbit ileum, is pharmacologically identical to the OP4 sites of other species mouse, rat, guinea pig, man., since the potencies p A2 values. of the pure and competitive antagonist wNphe1xnociceptin-1\u201313.NH2 is very similar to the values obtained in the other species. Moreover, the rabbit ileum is one of the few isolated organs that allow classifying compounds, which interact with OP4 receptors as full agonists, partial agonists, or pure antagonists

In vivo characterization of B-2 receptors mediating hypotension in anesthetized rabbits and guinea pigs

With the discovery of suitable pharmacologic tools for B 2 receptor characterization, it has been demonstrated in vitro that the pharmacological spectrum of this receptor type obtained in various organs (e.g. intestine, vessels, urogenital tract) remains the same within the species but may show marked differences among species (e.g. the rabbit, the guinea pig) (Regoli et al., 1993; Regoli et al., 1994). Thus, orders of potency of agonists in rabbit and guinea pig tissues are opposite in that [Hyp3]BK is approximately 50- 100 times more potent than [AibT]BK in the rabbit and inversely, the latter compound is 2-10 times more active than [Hyp3]BK in the guinea pig. Furthermore, competitive antagonists, such as DArg[Hyp3,d-PheV,LeuS]BK and WIN 64338 (a nonpeptide compound), have also shown differences in their ability to block bradykinin responses in these two species while HOE 140, a non-competitive and long-acting antagonist, shows equipotent activities on both. Based on these results, we have suggested that B 2 receptors may be pharmacologically subject to interspecies variability. The present study was designed to find out if results obtained in vitro can be reproduced in vivo by measuring pharmacological parameters (namely EDs0 for agonists and ICso for antagonists) on kinin-induced blood pressure changes in the rabbit and the guinea pig

Kinin receptors in the diabetic mouse

It has been proposed that kinins are important inflammatory mediators involved in the pathogenesis of several diseases. In the present study, we attempted to determine the effects of kinins in a type I diabetic mouse model, using in vitro assays. Injection of streptozotocin (STZ) to the C57BL/Ks mdb mice causes an insulitis (inflammation of Langerhans islets) that leads to the diabetic condition. Ten days following the STZ treatment, the mice showed increased glycemia. We examined the effect of kinins and other agents (substance P, neurokinin A, acetylcholine) on the stomach fundus and urinary bladder of control and diabetic mice. Our results show that the sensitivity of the stomach fundus to bradykinin (BK) and desArg9BK (DBK), but not to other contractile agents, was substantially increased in the tissues of diabetic mice. The maximal contractions induced by BK and DBK were increased 1.5- to 2-fold in the stomachs from diabetic mice compared with those from normal mice. BK induced similar maximal contractions of urinary bladder strips from normal or STZ-treated mice, while DBK did not show any effect on this preparation. Interestingly, the apparent affinities of all agonists are similar in the two groups, normal and diabetic. These results suggest that B, and B, receptors are overexpressed in the stomach fundus but not in the urinary bladder of diabetic mice

Solution conformation of nociceptin

Nociceptin, a novel heptadecapeptide, interacts with ORL1 a G protein-coupled receptor whose sequence is closely related to that of the kappa opioid receptor but has no opioid activity. We have investigated the conformational preferences of Nociceptin also in comparison to Dynorphin A. The N-terminal part of Nociceptin has the same conformational preferences of the message of endogenous opioids but the C-terminal part of the sequence is more flexible than the corresponding address of Dynorphin A. [Tyr1]-Nociceptin, while retaining nociceptive activity, has also an opioid activity comparable to that of enkephalins