Pharmacological characteristics of bombesin receptor mediating hypothermia in the central nervous system of rats

Tsushima, Hiromi; Mori, Mayumi; Fujiwara, Nakako; Moriyama, Akihiko

doi:10.1016/s0006-8993(03)02281-9

Cited by 24 publications

(20 citation statements)

References 31 publications

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“…Effective concentrations of BIM in the current experiment were comparable to or below concentrations reported to be effective in other in vivo neural models [4,24,38,47]. In the current experiment, BIM was effective when administered 90 min, but not 30 min, before the 5-HT receptor agonists.…”

Section: Discussionsupporting

confidence: 73%

“…In the current experiment, BIM was effective when administered 90 min, but not 30 min, before the 5-HT receptor agonists. Although comparable time comparisons have not been examined in prior studies, in most in vivo work, at least 30 min have been allowed to elapse before the effects of the PKC inhibitor have been assessed [4,24,38,47]. Thus the current time-dependency is consistent with prior findings and is likely to reflect the time required for the inhibitor to effectively block DOI's ability to increase PKC.…”

Section: Discussionsupporting

confidence: 67%

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The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior

Selvamani

Lincoln

Uphouse

2007

Behavioural Brain Research

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Ovariectomized rats with bilateral cannulae near the ventromedial nucleus of the hypothalamus were hormonally primed with 10μg estradiol benzoate and 500μg progesterone. Sexually receptive females were infused bilaterally with 200 ng of the 5-HT 1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), or with a combination of 200 ng 8-OH-DPAT and 2000 ng of the 5-HT 2 receptor agonist, (±)-2,5-dimethoxy-4-iodophenyl-2-aminopropane HCl (DOI). 8-OH-DPAT inhibited lordosis behavior and DOI reduced this inhibition. However, if females were preinfused with the PKC inhibitor, bisindolymaleimide I hydrochloride (BIM), DOI's effect was eliminated. BIM's attenuation of the effects of DOI was time-dependent. When BIM was infused 90 min, but not 30 min, before the 5-HT receptor agonists, BIM eliminated DOI's protection against the lordosisinhibiting effects of 8-OH-DPAT. A concentration of BIM as low as 10 −5 nmol in a 0.5μl infusion volume was effective and there was little evidence of dose responsivity between 10 −5 and 10 −1 nmol of BIM. In contrast, prior infusion with vehicle or with 10 −7 nmol BIM had no impact on the female's response to the 5-HT receptor agonists. These findings allow the suggestion that DOI's ability to increase PKC may be responsible for attenuation of the effects of 8-OH-DPAT on lordosis behavior. KeywordsPKC inhibitor; 5-HT 1A receptors; 5-HT 2 receptors; ovariectomized; sexual behavior IntroductionWithin the ventromedial nucleus of the hypothalamus (VMN), serotonin (5-HT) modulates female rat sexual behavior by acting on multiple 5-HT receptors [39]. Lordosis behavior, a supraspinal estrogen-dependent reflex of sexually receptive females [29], is inhibited by 5-HT 1A receptor agonists and facilitated by 5-HT 2 receptor agonists and their coactivation attenuates the lordosis-inhibitory effects of 5-HT 1A receptor agonists [39]. We have proposed that this 5-HT 1A /5-HT 2 receptor interaction enables the female to fine-tune her behavior so that it is most adaptive to environmental conditions [42]. However, the mechanisms for this interaction are not known.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionsupporting

confidence: 67%

The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior

Selvamani

Lincoln

Uphouse

2007

Behavioural Brain Research

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“…2), IL-1β and Bom act as pyrogenic and hypothermic drugs, respectively. 22,24) In all of the high-fat diet and ND groups, IL-1β increased BT with two peaks. Because the first coinciding with drug administration were also observed after the injections of vehicle, the second were caused by IL-1β, which showed statistically significant increases in BT, compared with BT after vehicle administration in each groups (Figs.…”

Section: Effects On Growthmentioning

confidence: 99%

“…[22][23][24] The coordinate of the lateral cerebroventricle was determined using the atlas of Konig and Klippel.…”

mentioning

confidence: 99%

Long-term High-Soybean Oil Feeding Alters Regulation of Body Temperature in Rats

Tsushima

Yamada

Miyazawa

et al. 2014

Biological & Pharmaceutical Bulletin

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We investigated whether body temperature (BT) regulatory mechanisms are influenced by dietary fatty acids (FA). Male Wistar rats were fed a high-fat diet containing fish oil (HFD), soybean oil (HSD) or lard (HLD). At the 20-week intervention, the BT of the HSD and HLD groups were lower than that of the normal diet (ND) group in the light and dark periods. The intracerebroventricular injections of interleukin-1β and bombesin in the HSD group induced greater hyperthermia and weaker hypothermia, respectively, than in the ND group. The HSD differentially affected BT under both physiological and pharmacological conditions. In the hypothalamus, the ratio of n-6/n-3 FAs was higher in the HSD group compared with the ND group. DNA microarrays revealed increased expression of thyroid-stimulating hormone β-subunit, and decreased expression of several genes in the hypothalamus of the HSD group compared with the ND group. The HSD feeding increased several adipokine concentrations in the plasma. However, there were no adipokines or gene expressions that changed in only the HSD and HLD groups showing significant hypothermia under the physiological condition. These findings suggested that long-term HSD intake produces abnormal BT regulation. It is less likely that adipokines or proteins/peptides are involved in abnormal BT regulation under the physiological conditions after HSD feeding.Key words body temperature; hypothalamus; high-fat diet; interleukin (IL)-1β; bombesinWe now obtain more energy from fat and glucose than ever before. These changes have induced hyperlipidemia and adipocyte hypertrophy, resulting in the risk of cardiovascular diseases, diabetes mellitus and obesity. From this point of view, there are many reports on lipid and/or glucose metabolisms during high-fat diet feeding in living animals.

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“…reduced the analgesic effect of gabapentin on mechanical hypersensitivity, suggesting that mechanisms other than presynaptic removal of GABAergic inhibition of LC neurons may partly contribute to the supraspinally mediated analgesic effects of gabapentin. However, we consider that this dose of chelerythrine (10 μg) should be enough to block PKC when applied locally in rodents (14,15). Further studies will be needed to clarify the supraspinal PKC-dependent cellular mechanisms employed by gabapentin.…”

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confidence: 98%

Protein Kinase A–Dependence of the Supraspinally Mediated Analgesic Effects of Gabapentin on Thermal and Mechanical Hypersensitivity

et al. 2009

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Abstract. We have recently shown that gabapentin generates protein kinase A (PKA)-dependent presynaptic inhibition of GABAergic synaptic transmission in locus coeruleus (LC) neurons only under neuropathic states. To verify behaviorally this in vitro electrophysiological finding, the PKA inhibitor H-89 was injected intracerebroventricularly (i.c.v.) before supraspinal application of gabapentin in mice developing thermal and mechanical hypersensitivity after peripheral nerve injury. H-89 dose-dependently attenuated the analgesic effects of i.c.v.-injected gabapentin, suggesting that PKA-dependent removal of GABAergic inhibition of LC neurons is the most plausible synaptic mechanism underlying the supraspinally mediated analgesic effects of gabapentin involving activation of the descending noradrenergic pain-inhibitory system. Keywords: neuropathic pain, gabapentin, protein kinase A (PKA)The anti-hypersensitivity actions of gabapentin have been well established, although we are still on the way to full understanding of its underlying mechanisms. We have been focusing on the supraspinal structure as a possible site for its action and have demonstrated that intracerebroventricular (i.c.v.) administration of gabapentin indeed decreases thermal and mechanical hypersensitivity by activating the descending noradrenergic system in a murine chronic pain model involving partial ligation of the sciatic nerve (1 -3). Our conclusions are supported by Hayashida et al. (4) who have observed recruitment of the descending noradrenergic system by gabapentin in both animal and human postoperative pain conditions. Our recent electrophysiological experiments have shown that gabapentin presynaptically reduces GABAergic inhibitory postsynaptic currents (IPSCs) in locus coeruleus (LC) neurons in slices taken from mice only after peripheral nerve injury (5), thereby removing inhibitory influences on LC neurons, leading to activation of the descending noradrenergic system to relieve neuropathic pain. Recent lines of evidence indicate that several protein kinases including PKC and PKA play crucial roles in mediating not only the pathophysiology of chronic pain after nerve injury or inflammation, but also the hyperalgesia-dependent pharmacological actions of gabapentin (6, 7). Interestingly, our in vitro electrophysiological study demonstrated that the PKA inhibitor H-89, but not the PKC inhibitor chelerythrine, abolished the inhibitory action of subsequently superfused gabapentin on IPSCs in LC neurons in slices taken from mice after peripheral nerve injury, suggesting that PKA activity plays an important role in supraspinal gabapentin responsiveness in neuropathic conditions. The aim of the present study was to behaviorally verify this in vitro electrophysiological finding (5).All of the experimental protocols were approved by the Animal Care and Use Committee of Nagoya City University, and were carried out according to the guidelines of the National Institutes of Health and The Japanese Pharmacological Society.We employed a murine neurop...

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Pharmacological characteristics of bombesin receptor mediating hypothermia in the central nervous system of rats

Cited by 24 publications

References 31 publications

The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior

The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior

Long-term High-Soybean Oil Feeding Alters Regulation of Body Temperature in Rats

Protein Kinase A–Dependence of the Supraspinally Mediated Analgesic Effects of Gabapentin on Thermal and Mechanical Hypersensitivity

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