家兔中脑导水管周围灰质中注射八肽胆囊收缩素（CCK—8）拮抗吗啡镇痛和...

We have reported that intracerebroventricular (i. c. v.) injection of 1-4 ng of CCK-8 to the rat produced a remarkable antagonistic effect on morphine analgesia. In order to study the species specificity and the site of action, CCK-8 was microinjected into the PAG of the rabbit, and its influence on morphine analgesia and electroacupuncture analgesia was observed. The latency of the escape response (ERL) to radiant heat focused on the snout was measured as an index of the pain threshold. Microinjections were made via cannulae chronically implanted into the PAG. The drug solutions were delivered in a volume of 1 microliter, at a speed of 0.125 microliter/min. The ERL was measured for a period of 60 or 70 minutes at 10 min intervals. 1. CCK-8 administered unilaterally to the PAG of the rabbit at a dose of 3 ng antagonized the analgesia induced by morphine (4 mg/kg, i. v.) by 73% (P less than 0.001), and reduced the analgesic effect of electroacupuncture by 67% (P less than 0.001). These effects were dose-dependent within the range from 1.5 ng to 6.0 ng. The effect of CCK-8 was reversed by CCK receptor blocker proglumide (4 microliters, intra-PAG injection). Unsulfated CCK-8 (CCK-us) had no effect in this regard. These results indicate that in the PAG of the rabbit, exogenously administered CCK-8 was capable of antagonizing opioid analgesia by the activation of CCK receptors. 2. Two groups of rabbits were given with morphine (2 mg/kg, i. v.) and simultaneous injection of CCK-8 antiserum (CCK-AS, 1 microliter) or normal rabbit serum (NRS) into the PAG.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vivo and in vitro effects of cholecystokinin octapeptide on the release of growth hormone in rats

The effect of cholecystokinin octapeptide (CCK-8) on the release of growth hormone (GH) in rats was studied in vivo and in vitro. Intravenous injection of 5 micrograms/100 g BW of CCK-8 resulted in significant increase in the plasma GH level after 10 and 20 min. CCK-8 at concentrations of 10(-11)M to 10(-7)M also caused dose-dependent stimulation of GH release from dispersed cells of rat anterior pituitary. On the other hand, somatostatin (SRIF) inhibited GH release from dispersed cells of rat anterior pituitary in a dose-related manner at concentrations of 10(-7)M to 10(-9)M. Release of GH from the cells was increased by addition of K+ at high concentration (50 mM) in a Ca++-dependent manner. Addition of 10(-3)M verapamil to the incubation medium inhibited CCK-8-induced GH release from the cells. Addition of SRIF (10(-7)M) to the incubation medium inhibited GH release from the cells induced by CCK-8 or high K+ (50 mM). These results indicate that CCK-8 acts directly on the anterior pituitary cells to stimulate GH release and that calcium ion is involved in the mechanism of this effect.     

Influence of cholecystokinin on central monoaminergic pathways

Dopamine (DA) and cholecystokinin octapeptide carboxy-terminal (CCK-8) have been found to coexist in some mesolimbic neurons. The present investigation was undertaken in order to study the biochemical and behavioral interactions between CCK-8 and some central monoaminergic pathways. The action of the sulfated form of CCK-8 (10 micrograms/10 microliter intracerebroventricularly) on DA turnover in nucleus accumbens, olfactory tubercles and corpus striatum of the rat was determined after DA synthesis inhibition with alpha-methyl-p-tyrosine (250 mg/kg i.p.). Also, CCK-8 action (1-30 micrograms intracisternally) on DA synthesis was assessed by measuring accumulation of dihydroxyphenylalanine (DOPA) after DOPA-decarboxylase inhibition with NSD-1015 (m-hydroxybenzylhydrazine, 100 mg/kg i.p.). The contents of DA and its main metabolites, dihydroxyphenylacetic acid and homovanillic acid, together with serotonin and its main metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were measured in different brain areas after direct injection of CCK-8 into the ventral tegmental area (A10) or nucleus accumbens. Further, the effect of CCK-8 on amphetamine-induced locomotion and apomorphine-induced stereotypies was studied along with changes in spontaneous locomotion and rearing after CCK-8 injection into the ventral tegmental area and nucleus accumbens. No consistent statistically significant effects of CCK-8 on biochemical or behavioral assessments on measures of DA function were observed. However, injection of high doses of CCK-8 into the ventral tegmental area significantly decreased levels of 5-HIAA in the nucleus accumbens, olfactory tubercles and striatum.     

Cholecystokinin octapeptide releases growth hormone from the pituitary in vitro

Cholecystokinin-octapeptide (CCK-8)(10^?6 to 10^?8M) produced a marked increase in growth hormone (GH) release from incubated rat anterior pituitary quarters and from cultured GH₃ pituitary tumor cells. Although several CCK-8 analogues also caused GH release, bombesin, secretin and pancreatic polypeptide had no effect on GH secretion $\text{in vitro}$. In the GH₃ cell line, CCK-8 (10^?7M) reversed the inhibitory effect of somatostatin (10^?5M) on GH release. As CCK immunoreactivity has been demonstrated to be present in the hypothalamus, these results suggest that CCK-8 may be a physiologically important growth hormone releasing factor.     

Effect of peripheral administration of cholecystokinin on food intake in apolipoprotein AIV knockout mice

Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are satiation factors secreted by the small intestine in response to lipid meals. Apo AIV and CCK-8 has an additive effect to suppress food intake relative to apo AIV or CCK-8 alone. In this study, we determined whether CCK-8 (1, 3, or 5 μg/kg ip) reduces food intake in fasted apo AIV knockout (KO) mice as effectively as in fasted wild-type (WT) mice. Food intake was monitored by the DietMax food system. Apo AIV KO mice had significantly reduced 30-min food intake following all doses of CCK-8, whereas WT mice had reduced food intake only at doses of 3 μg/kg and above. Post hoc analysis revealed that the reduction of 10-min and 30-min food intake elicited by each dose of CCK-8 was significantly larger in the apo AIV KO mice than in the WT mice. Peripheral CCK 1 receptor (CCK1R) gene expression (mRNA) in the duodenum and gallbladder of the fasted apo AIV KO mice was comparable to that in WT mice. In contrast, CCK1R mRNA in nodose ganglia of the apo AIV KO mice was upregulated relative to WT animals. Similarly, upregulated CCK1R gene expression was found in the brain stem of apo AIV KO mice by in situ hybridization. Although it is possible that the increased satiating potency of CCK in apo AIV KO mice is mediated by upregulation of CCK 1R in the nodose ganglia and nucleus tractus solitarius, additional experiments are required to confirm such a mechanism.     

Interaction of apolipoprotein AIV with cholecystokinin on the control of food intake

Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are peptides that act both peripherally and centrally to reduce food intake by decreasing meal size. The present study examined the effects of intraperitoneally administered bolus doses of recombinant apo AIV, CCK-8, and a combination of subthreshold doses of apo AIV and CCK on 4-h food intake in rats that were fasted overnight. Apo AIV at 100 microg/kg reduced food intake significantly relative to the saline control for 1 h, as did doses of CCK-8 at or above 0.125 microg/kg. Doses of apo AIV (50 microg/kg) or CCK (0.06 microg/kg) alone had no effect on food intake. However, when these subthreshold doses of apo AIV and CCK were administered together, the combination produced a significant inhibition of food intake relative to saline controls (P < 0.001), and the duration of the effect was longer than that caused by the administration of either apo AIV or CCK alone. The satiation effect produced by CCK-8 + apo AIV was attenuated by lorglumide, a CCK1 receptor antagonist. We conclude that, whereas the intraperitoneal administration of doses of either recombinant apo AIV or CCK at or above threshold levels reduces food intake, the coadministration of subthreshold doses of the two peptides is highly satiating and works via CCK1 receptor.     

Specificity of nucleus accumbens to activities related to cholecystokinins in rats

Cholecystokinin octapeptide (CCK-8) or cholecystokinin tetrapeptide (CCK-4) were bilaterally injected into the areas where dopamine (DA) terminals and receptors have been detected; nucleus accumbens (NA), nucleus caudatus (NC), medial profrontal cortex (MPC), or prefrontal cortex (PC). The amount injected to each animal varied from 0 (control), 1 to 500 ng of CCK-8 and 0 (saline control), 0.5 to 2.5 micrograms of CCK-4 in NA in a volume of 1 microliter. The other areas received 500 ng CCK-8, 2.5 micrograms CCK-4 and proper control injections. The effects were observed in an open-field apparatus by measuring locomotor and rearing responses, the latency to move out of a specified area where the animal was first placed, and the amount of excretory bolus during a 5 min period following injections. When injected into NA, CCK-8 decreased locomotion and rearing at doses of 2.5 ng or more in a dose-related manner whereas CCK-4 increased locomotion and rearing at 1 microgram or more. The effects on latency and defecation were not detected. When the peptides were injected into NC, MPC or PC no effects were detectable. It appears that the effects of CCK-8 and CCK-4 on the exploratory responses are site-specific at NA where CCK-8 and DA are found to coexist in same neurons. CCK-4, a metabolite of CCK-8, could exert a negative feedback to moderate the effect of CCK-8.     

Effect of cholecystokinin octapeptide sulphate ester on brain monoamines in the rat

The effect of different doses of intracerebro-ventricularly administered cholecystokinin octapeptide sulphate ester (CCK-8-SE) was studied on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) contents in the hypothalamus, mesencephalon, amygdala, septum and striatum, 10, 20 and 60 min following administration. The DA and NE content increased and the 5-HT content decreased in the hypothalamus and mesencephalon. A biphasic action was observed in the amygdala of DA, NE and 5-HT depending upon the time and doses used. Similar action was seen on DA and NE in the septum. In the striatum, the DA and 5-HT content decreased while the NE level first increased and then decreased. The data indicate that the CCK-8-SE is able to modify the activity of DA, NE and 5-HT in different brain regions in a time and dose-dependent manner, with a local specific action.     

Subcortical limbic3H-N-propylnorapomorphine binding sites are markedly modulated by cholecystokinin-8 in vitro

By means of the dopamine (DA) agonist radio ligand 3H-N-propylnorapomorphine (3H-NPA) the effects of cholecystokinin-8 (CCK-8) have been evaluated in vitro on the binding characteristics of the DA agonist sites in membrane preparations from the subcortical limbic forebrain containing mainly nucleus accumbens and tuberculum olfactorium. It was shown that CCK-8 (10(-8) M) can produce a 40% increase in the KD value of the 3H-NPA binding sites and a significant 10% increase in the Bmax values of these sites. It is therefore suggested that there exist marked receptor-receptor interactions between the CCK-8 binding sites and DA agonist binding sites in the limbic forebrain. On the basis of these findings and in view of the fact that CCK peptides are comodulators in certain types of mesolimbic DNA neurons but cannot modulate DA release in these DNA synapses, the hypothesis is introduced that the presence of DA comodulators such as CCK-8 in the DA synapses makes possible a heterostatic regulation of the synapse. Thus, by means of receptor-receptor interactions, peptide comodulators may change the set point of the main transmission line without inducing homeostatic feedback responses on synthesis and release of the main transmitter, opening up a new way to modulate chemical transmission in general.     

Effects of cholecystokinin peptides and neurotensin on dopamine release and metabolism in the rostral and caudal part of the nucleus accumbens using intracerebral dialysis in the anaesthetized rat

By means of intracerebral microdialysis effects of cholecystokinin peptides and neurotensin administered via the microdialysis probe have been studied on dopamine release and metabolism in the nucleus accumbens and neostriatum of the halothane anaesthetized male rat. Levels of extra cellular dopamine (DA) and its metabolites 3,4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were assessed in nuc. accumbens (rostral and caudal part) using high performance liquid chromatography in combination with electrochemical detection.

(1) In the rostral part of the nuc. accumbens CCK-8 (10 and 100 μM), CCK-33 (100 μM) but not CCK-4 (10 and 100 μM) increased the levels of DA in the perfusate without increasing the extracellular levels of DOPAC and HVA. (2) In the caudal nuc. accumbens CCK-8 and CCK-4 in concentrations of 10 μM and 100 μ M of CCK-33 had no effect on DA release and metabolism, since the extracellular levels of DA, DOPAC and HVA were not changed. (3) In the rostral nuc. accumbens perfusion with 10 μM of neurotensin but not with any other concentration of neurotensin (0.01, 0.1, 1 and 100 μM) increased the levels of DA in the extracellular fluid. (4) In the caudal nuc. accumbens a 40 min perfusion with neutrotensin produced a concentration dependent increase of the levels of DA in the perfusate (peak action at 10 μ M) which in this case was associated with increases in the extracellular levels of DOPAC and HVA. (5) By means of receptor autoradiography using (3-[¹²⁵I]iodotyrosyl³) neurotensin it was found that a 40 min perfusion with this radioligand in the rostral nuc. accumbens reached a total volume of 0.051 mm³. The diffusion of the radioligand was limited to the rostral or caudal part of the nuc. accumbens depending upon the site of placement of the dialysis probe.

The results indicate the existence of cholecystokinin (CCK) receptors in the rostral nuc. accumbens, which are sensitive to CCK-8 and CCK-33 but not to CCK-4, and which facilitate DA release without producing any detectable increase in DA metabolites. In contrast, such receptors do not appear to play a similar role in the regulation of DA release in the caudal nuc. accumbens, where DA terminals contain CCK-like immunoreactivity. Furthermore, the results indicate that neurotensin receptors exist both in the rostral and caudal nuc. accumbens, where they inter alia enhance the release of DA. In the caudal nuc. accumbens these effects of neurotensin are also associated with an increase of DA metabolites, possibly suggesting that in this region neurotensin receptors may also control DA synthesis.     

Influence of cholecystokinin on the synaptosomal dopamine uptake in the nucleus accumbens of rats

The influence of the sulfated cholecystokinin octapeptide (CCK-8S) on the synaptosomal high-affinity [³H]dopamine (DA) uptake was investigated in the medial and lateral part of nucleus accumbens in rats. CCK-8S induced a concentration-dependent biphasic inhibition of [³H]-DA uptake in both subregions. After preincubation of CCK-8S with the synaptosomes the inhibitory effect was completely abolished. Kinetic analysis of the uptake influence suggests an uncompetitive inhibition by CCK-8S; this means that CCK-8S attacks only the DA-uptake carrier complex by inhibitory manner. The possible regulatory relevance of this mechanism is discussed.     

Effects of the CCK-A receptor antagonist CR 1409 on the activity of rat midbrain dopamine neurons

Previous studies have shown that acute intravenous treatment with sulfated cholecystokinin octapeptide (CCK-8S) but not unsulfated CCK-8 increases the number of spontaneously active midbrain dopamine (DA) neurons. This suggested that a peripheral-type (CCK-A) CCK receptor mediates this effect. Proglumide does not discriminate between CCK-A and CCK-B (central-type) receptors. In the present study, rats were treated acutely or repeatedly (14 days) with the selective CCK-A antagonist CR 1409. Repeated treatment with 5 mg/kg (IP) increased the number of spontaneously active DA cells in the A10 (ventral tegmental area) but not the A9 (substantia nigra zona compacta) region, which suggests that these DA populations are differentially affected by prolonged CCK-A receptor blockade. The sensitivity of impulse-regulating DA autoreceptors to the DA agonist quinpirole was not altered by CR 1409.     

Acute norepinephrine reuptake inhibition decreases performance in normal and high ambient temperature.

Combined inhibition of dopamine (DA)/norepinephrine (NE) reuptake improves exercise performance and increases core temperature in the heat. A recent study demonstrated that this effect may primarily be related to increased DA activity. NE reuptake inhibition (NERI), however, has received little attention in humans, certainly in the heat, where central fatigue appears to be a main factor influencing performance. Therefore the present study examines the effect of NERI (reboxetine) on exercise capacity, thermoregulation, and hormonal response in normal and high temperature. Nine healthy well-trained male cyclists participated in this study. Subjects ingested either placebo (Pla; 2 x 8 mg) or reboxetine (Rebox; 2 x 8 mg). Subjects exercised in temperate (18 degrees C) or warm (30 degrees C) conditions and cycled for 60 min at 55% W(max) immediately followed by a time trial (TT; Pla18/Rebox18; Pla30/Rebox30) to measure exercise performance. Acute NERI decreased power output and consequently exercise performance in temperate (P = 0.018) and warm (P = 0.007) conditions. Resting heart rate was significantly elevated by NERI (18 degrees C: P = 0.02; 30 degrees C: P = 0.018). In Rebox18, heart rate was significantly higher than in the Pla18, while in the heat no effect of the drug treatment was reported during exercise. In Rebox30, all hormone concentrations increased during exercise, except for growth hormone (GH), which was significantly lower during exercise. In Rebox18, prolactin (PRL) concentrations were significantly elevated; GH was significantly higher at rest, but significantly lower during exercise. In conclusion, manipulation of the NE system decreases performance and modifies hormone concentrations, thereby indicating a central NE effect of the drug. These findings confirm results from previous studies that predominantly increased DA activity is important in improving performance.     

Cholecystokinin receptor mediated hydrolysis of inositol phospholipids in guinea pig gastric glands

CCK-octapeptide (CCK-8) (EC50 = 0.5 nM), in the presence of Li+, increased 3H-inositol phosphate (IP) accumulation in guinea pig gastric glands prelabeled with 3H-inositol. CCK-8 desulfate, human gastrin I and pentagastrin were much less potent than CCK-8. Antagonists of CCK receptors such as proglumide, dibutyryl-c-GMP and CBZ-Tyr (SO3H)-Met-Gly-Trp-Met-AspNH2 shifted the CCK dose response curve to the right. However, histamine (H1 and H2), cholinergic, substance P and alpha- and beta-adrenergic receptor antagonists had no effect on 3H-IP accumulation induced by CCK. The results suggest that CCK receptor activation in gastric glands leads to an enhanced breakdown of inositol phospholipids which may relate to calcium mobilization and pepsinogen secretion.     

促性腺激素释放激素及多巴胺对斜带石斑鱼生长激素分泌及其mRNA表达的调控

研究斜带石斑鱼生长激素分泌及其mRNA表达的调控规律对于性别分化的控制、临床药物的选择,以及石斑鱼的增养殖等均具有重要的理论意义和实践意义。本文应用静态孵育系统,采用放射免疫测定法和化学发光液相杂交实验,研究GnRH和DA对斜带石斑鱼GH分泌、GHmRNA合成的调控作用。100nmol／LsGnRH作用斜带石斑鱼脑垂体碎片1也4h,明显促进GH的释放和GHmRNA的合成,并具有时间依存性;10nmol／L～1μmol／LsGnRH作用1h能明显促进斜带石斑鱼脑垂体释放GH,促进GHmRNA的合成,表现出明显的剂量效应。100nmol／L、1μmol／LmGnRH作用1h以一定的剂量依存方式促进GH的释放、促进GHmRNA的合成,但mGnRH的效应比相应剂量的sGnRH的作用弱。APO为DA受体的非选择性激动剂,不同剂量APO对斜带石斑鱼脑垂体碎片的作用结果显示,10nmol／L-1μmol／L APO以剂量依存方式促进斜带石斑鱼脑垂体碎片释放GH、促进GHmRNA的合成：1μmol／LAPO作用12h以上明显促进GH的释放和GHmRNA的合成,并随时间的延长而增加。与sGnRH对斜带石斑鱼GH释放、GHmRNA合成的作用相比,APO的作用较弱。本文研究结果证实GnRH和DA能促进斜带石斑鱼脑垂体GH释放和GHmRNA合成。     

Pharmacological examination of cholecystokinin (CCK-8)-induced contractile activity in the rat isolated pylorus

The actions of cholecystokinin (CCK) in the production of a satiety-like state have been suggested to be mediated via receptors for CCK which are located in the pylorus. We investigated the actions of CCK and other pharmacological agents upon the isolated rat pylorus in vitro. We used the change in isometric tension of the tissue preparation (contraction amplitude) as the measure of the effects of the pharmacological agents. Cholecystokinin COOH-terminal octapeptide (CCK-8) was observed to elicit contraction in a dose-dependent manner, with the half-maximal dose (ED50) in the vicinity of 1 nM. Rapid desensitization to CCK was observed. The contraction amplitude was atropine-independent, and was not significantly antagonized by a wide variety of other pharmacological agents. The Na+-channel blocker tetrodotoxin was without effect upon contractile amplitude, as was the K+-channel blocker 4-aminopyridine, except at very high concentrations. Neurotensin, bombesin, and the substance P and bombesin antagonist spantide all elicited contraction in the isolated tissue; neurotensin had a similar potency to CCK-8 and bombesin was 10-15-fold less potent than CCK-8. Unsulfated CCK-8 was at least 170-fold less potent than sulfated CCK-8 and tetragastrin was at least 500-fold less potent than CCK-8. These results suggest that pyloric CCK receptors, which appear to have a pharmacological profile typical of peripheral CCK receptors, may have a physiological role in the peptidergic control of gastric emptying in the rat.     

Hormonal regulation of expression of the endogenous and transfected human growth hormone gene

Expression of the endogenous human GH (hGH) gene in response to glucocorticoids, thyroid hormone, and insulin was studied in cultures of dispersed GH-secreting human pituitary adenomas. Results were compared to those obtained when the hGH gene was transfected into rat pituitary tumor cells (GC). In the human pituitary cells the glucocorticoid dexamethasone [(Dex) 10(-6) M] increased the release of GH and the levels of GH mRNA by 2 to 4-fold (P less than 0.05). T3 (10(-8) M) had no effect on GH mRNA but increased hGH release by 2- to 6-fold (P less than 0.01). Insulin (5 x 10(-9) M) alone had no significant effect on either hGH mRNA or protein, but blunted the effect of Dex. Among 11 of 18 GC cell clones transfected with the hGH gene with detectable hGH mRNA expression, Dex increased hGH mRNA levels in seven and T3 treatment reduced hGH mRNA levels in eight. Conversely, rat GH mRNA levels from the endogenous rat gene were increased by either Dex or T3 in all 18 clones. Insulin alone or in combination with T3 or Dex was found to increase hGH mRNA levels in some cell lines and to decrease hGH mRNA levels in others; these effects were correlated strongly (r = 0.88; P less than 0.001) with the influence of insulin on the endogenous rat GH gene, implying that individual cellular differences can simultaneously affect the insulin responsiveness of both genes.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vivo growth hormone (GH) response to human GH-releasing factor (GRF) or somatostatin (SRIF) in foetal pigs.

The short-term effect of hypothalamic GRF and SRIF on the pituitary release of GH at different stages of gestation has been studied. In the present experiment eighteen gilts were used, six at each of 66, 88 and 110 days of gestation. Ventral laparotomy was performed under general anaesthesia and a section of uterus was exteriorized. Blood samples were obtained from the umbilical vein of three foetuses per gilt just prior to the injection of each foetus with either saline, 5 micrograms/kg of hGRF (1-44)NH2 or 50 micrograms/kg of SRIF into the umbilical vein. Additional blood samples were obtained 15, 30, 45 and 60 min post-injection. Serum samples were radioimmuno-assayed for GH (porcine). There was a treatment by gestational age interaction (P less than 0.01) on mean GH concentrations, area under the GH curve and GH peaks. While treatments had no effect (P greater than 0.1) on GH variables at 66 days of gestation, the area under the GH curve was slightly increased by GRF (P = 0.14) at day 88 and all GH variables were significantly increased (P less than 0.01)) by GRF at 110 days of gestation. There was a quadratic effect of time post-injection on GH concentrations at 88 (P less than 0.05) and 110 (P less than 0.001) days of gestation. There was no effect of SRIF injection (P greater than 0.1) on GH concentrations at any gestational age. In conclusion, the foetal pituitary responsiveness to GRF develops with foetal age and is maximal at the end of gestation, whereas there is no short-term response to a bolus of SRIF at any stage of gestation.     

A method for studying synaptosomal release of neurotransmitter candidates, as evaluated by studies on cortical cholecystokinin octapeptide release

A method for perfusing rat cortical synaptosomes for studying the regulation of cholecystokinin octapeptide (CCK-8) release has been developed and was found to have advantages over the static incubation system. Synaptosomes isolated from rat cortex were suspended in Biogel P2 columns and perfused with Krebs Ringer Bicarbonate buffer. One hundred mM KCl and 75 microM veratine stimulated CCK-8 release, which was Ca++-dependent. The synaptosomes were functionally viable for at least 135 min of incubation as indicated by multiple 100 mM KCl depolarizations and uptake of (3H)-norepinephrine and (14C)-choline. Dopamine and acetylcholine (10(-6)M) stimulated CCK-8 release while serotonin and norepinephrine were without effect. Approximately 20% of total occluded CCK-8 was released from synaptosomes by 100 mM KCl and degradation of CCK-8 was less than 10%. Perfusion of synaptosomes has several advantages over static incubation systems and allows systematic studies on the role of neurotransmitter in the regulation of neuropeptide secretion.     

Growth hormone and prolactin secretion after metoclopramide administration (DA2 receptor blockade) in fertile women.

In this report, we will describe the results of a cross-sectional study to assess PRL and GH secretion during the early follicular phase in 22 fertile patients after metoclopramide administration in order to achieve a dopaminergic DA2 receptor blockade. Blood samples were collected at - 15, 0, 15, 30, 45 and 60 minutes. PRL, GH, estradiol, IGF-I, TSH, glucose, and insulin were measured in the samples taken at - 15 and 0 minutes. The existence of a correlation between GH and PRL secretion was investigated. All patients presented normal serum levels of estradiol, prolactin, insulin, fasting glucose and IGF-I. Serum GH levels were not changed after metoclopramide infusion (p = 0.302), but there was a significant alteration in serum PRL (p = 0.0001) with the highest levels after 30 (mean: 237.20 ng/ml +/- 95.86) and 45 (mean: 211.80 ng/ml +/- 83.24) minutes. Serum GH levels did not correlate with serum PRL levels after the dopaminergic DA2 blockade. We conclude that GH secretion was not modulated by a direct effect of type 2 dopamine receptor.