The Different Effects of I.c.v. Injection of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) on Prolactin Secretion in Adult Male and Lactating Rats

Tohei, Atsushi; Ikeda, Masashi; Hokao, Ryoji; Shinoda, Motoo

doi:10.1538/expanim.58.489

Cited by 6 publications

(5 citation statements)

References 21 publications

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“…To estimate the activity of serotonergic neurons in the brain after administration of cyclophosphamide, the concentration of 5HIAA in CSF was determined by high-performance liquid chromatography (HPLC) with electrochemical detection (ECD) [3,25,29]. The mobile phase (pH 3.0) consisted of 40 mM citric acid, 40 mM dibasic sodium phosphate, 0.08 mM EDTA, 7.5 mM sodium heptanesulphonate, 4% methanol, and 2% acetonitrile [23].…”

Section: Animals and Kaolin Preparationmentioning

confidence: 99%

Effects of Cyclophosphamide on the Kaolin Consumption (Pica Behavior) in Five Strains of Adult Male Rats

Tohei

Kojima

Ikeda

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. It is known that pica, the consumption of non-nutritive substances such as kaolin, can be induced by administration of toxins or emetic agents in rats. In the present study, we examined the effects of intraperitoneal (i.p.) administration of cyclophosphamide on pica behavior and on the concentration of 5-hydroxyindoleacetic acids (5HIAA) in cerebrospinal fluid (CSF) in the following five strains of adult male rats: Sprague Dawley (SD), Wistar, Fischer 344 (F344), Wistar-Imamichi (WI) and Long Evans (LE). Cyclophosphamide (25 mg or 50 mg/kg) was injected (i.p.) into the rats and kaolin and food intake were measured at 24 hr after injection. The animals were anesthetized with urethane (1 g/kg) at 3 hr after injection of cyclophosphamide, and CSF was collected from the cisterna magna. WI and LE rats clearly showed pica behavior as compared with the other strains. In LE rats, the concentration of 5HIAA in CSF also increased in a dose-dependent manner of cyclophosphamide. The pretreatment with ondansetron (5-HT 3 antagonist) restored both changes (kaolin consumption and 5HIAA levels) induced by cyclophosphamide. These results suggest that the LE rat is sensitive to cyclophosphamide, that pica induced by cyclophosphamide mimics many aspects of emesis including the serotonergic response in the central nervous system and that use of the pica model would be a practical method for evaluating the effects of antiemetic drugs in addition to the mechanism of emesis. Cancer chemotherapy with cyclophosphamide or cisplatin is usually associated with nausea or vomiting in humans [1,2,5,8,16]. These cytotoxic drugs can induce emesis in ferrets [8] and house musk shrews [14,20], and these two animal species have been often used in experiments for emesis. However, studies on the mechanisms of emesis in common laboratory animals such as rats and mice are limited due to the lack of vomiting reflex in rats and mice [8]. Although rats and mice do not vomit, they show pica behavior (the consumption of non-nutritive substances such as kaolin) in response to the various emetic stimuli [7,12,24,[30][31][32]. In rats, pica behavior can be induced by administration of cancer chemotherapy agents [11-13, 18, 22], lithium chloride [18,32], copper sulphate [32] and by motion exposure [7,24]. This behavior is recognized as an index of emesis, and the kaolin ingestion model can be used as a quantifiable behavioral assay of toxins [8,15]. In previous reports, Long Evans (LE) and Wistar rats were mainly used in experiments for pica behavior [11-13, 18, 22], but the reasons why these two strains have been used in this field of study are unclear. There has been no study comparing the expression of pica induced by any emetic stimuli among several strains of rats. In order to choose the best strain of rat for future pica research, we examined the effects of intraperitoneal (i.p.) administration of cyclophosphamide on pica behavior using Sprague Dawley (SD), Wistar, Fischer 344 (F344), Wistar-Imamichi (WI) and LE adult male rats in the present s...

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Section: Animals and Kaolin Preparationmentioning

confidence: 99%

Effects of Cyclophosphamide on the Kaolin Consumption (Pica Behavior) in Five Strains of Adult Male Rats

Tohei

Kojima

Ikeda

et al. 2011

The Journal of Veterinary Medical Science

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“…In mammals, VIP is well-documented as a stimulator for prolactin (PRL) release (Christian et al 2007) but the functional role of PACAP in PRL regulation is controversial and the data published are highly variable and contradictory to one another. For examples, the central effect via ICV injection of PACAP, which is inhibitory to PRL release in vivo (Tohei et al 2009), is different from the results of systemic administration (e.g., IV infusion) with either no effect (Sawangjaroen & Curlewis 1994) or stimulation on plasma PRL level (Jarry et al 1992). At pituitary level (e.g., in rat pituitary cells), the direct effect of PACAP on PRL regulation is also not consistent, as stimulatory (Benter et al 1995), inhibitory (Jarry et al 1992), and no effect has been reported (Hart et al 1992).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms for PACAP-induced prolactin gene expression in grass carp pituitary cells

Lin

Jiang

et al. 2017

Journal of Endocrinology

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In mammals, pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic hormone with diverse functions but its role in prolactin (PRL) regulation is highly controversial. To shed light on Prl regulation by PACAP in fish model, grass carp pituitary cells was used as a model to examine the receptor specificity and signal transduction for PACAP modulation of gene expression in the carp pituitary. Using RT-PCR, PACAP-selective PAC1 receptor was detected in carp lactotrophs. In carp pituitary cells, nanomolar doses of PACAP, but not VIP, could elevate Prl secretion and protein production with concurrent rise in mRNA and these stimulatory effects were blocked by PACAP antagonist but not VIP antagonist. PACAP-induced mRNA expression could be mimicked by activating adenylate cyclase (AC), increasing cAMP level by cAMP analog, or increasing intracellular Ca ([Ca]i) by Ca ionophore/voltage-sensitive Ca channel (VSCC) activator. PACAP-induced gene expression, however, was attenuated/abolished by suppressing cAMP production, inhibiting PKA activity, blocking [Ca]i mobilization and VSCC activation, calmodulin (CaM) antagonism, and inactivation of JNK and CaM Kinase II (CaMK-II). Similar sensitivity to CaM, JNK, and CaMK-II blockade was also noted by substituting cAMP analog for PACAP as the stimulant for mRNA expression. These results, as a whole, provide evidence for the first time that (i) PACAP activation of PAC1 receptor expressed in carp lactotrophs could induce Prl synthesis and secretion, and (ii) Prl production induced by PACAP was mediated by upregulation of gene expression, presumably via functional coupling of cAMP/PKA-, Ca/CaM-, and MAPK-dependent cascades.

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“…However, in sheep PACAP administered icv stimulated dopamine release from the tuberoinfundibular dopaminergic neurons and this effect was associated with a suppression of PRL level in the peripheral blood (138). Tohei et al (139) observed a similar effect after icv administration of PACAP to lactating rats exposed to suckling stimuli. PACAP38 decreased PRL secretion and increased the activity of thyrosin hydroxydase (TH) in ME of the pituitary stalk.…”

Section: The Effect Of Pacap On Prl Secretionmentioning

confidence: 96%

Current State of Understanding of the Role of PACAP in the Hypothalamo-Hypophyseal Gonadotropin Functions of Mammals

et al. 2020

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PACAP was discovered 30 years ago in Dr. Akira Arimura's laboratory. In the past three decades since then, it has become evident that this peptide plays numerous crucial roles in mammalian organisms. The most important functions of PACAP are the following: 1. neurotransmitter, 2. neuromodulator, 3. hypophysiotropic hormone, 4. neuroprotector. This paper reviews the accumulated data regarding the distribution of PACAP and its receptors in the mammalian hypothalamus and pituitary gland, the role of PACAP in the gonadotropin hormone secretion of females and males. The review also summarizes the interaction between PACAP, GnRH, and sex steroids as well as hypothalamic peptides including kisspeptin. The possible role of PACAP in reproductive functions through the biological clock is also discussed. Finally, the significance of PACAP in the hypothalamo-hypophysial system is considered and the facts missing, that would help better understand the function of PACAP in this system, are also highlighted.

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The Different Effects of I.c.v. Injection of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) on Prolactin Secretion in Adult Male and Lactating Rats

Cited by 6 publications

References 21 publications

Effects of Cyclophosphamide on the Kaolin Consumption (Pica Behavior) in Five Strains of Adult Male Rats

Effects of Cyclophosphamide on the Kaolin Consumption (Pica Behavior) in Five Strains of Adult Male Rats

Mechanisms for PACAP-induced prolactin gene expression in grass carp pituitary cells

Current State of Understanding of the Role of PACAP in the Hypothalamo-Hypophyseal Gonadotropin Functions of Mammals

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