Mizue Makimura

Acute and chronic intracerebroventricular morphine infusions affect long-term potentiation differently in the lateral perforant path.

Experiments were performed to investigate the effects of acute and chronic intracerebroventricular (icv) morphine infusions via osmotic minipumps on long-term potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of the rat dentate gyrus. Although significant antinociceptive activity was observed when morphine was infused (25 nmol/microl/h) for 30 min or 1 h, the activity was not observed in rats receiving morphine chronically for 72 h, and the tail-flick latency of this group was comparable to that of rats receiving saline. LTP induction was significantly attenuated after acute morphine infusion (1 h) in LPP-granule cell synapses of the dentate gyrus. In contrast, LTP induction was augmented after chronic morphine infusion for 72 h. Bath-perfused morphine augmented the baseline population spike (PS) amplitude in rats treated with saline, whereas it attenuated the LTP induced by chronic morphine infusion. Returning the LTP to the level of saline infusion after in vitro morphine perfusion suggests that enhancement of the LTP is a withdrawal-like phenomenon. These results suggest a difference between the effects of acute and chronic intracerebroventricular morphine infusions on synaptic plasticity in the LPP-granule cell synapses of the dentate gyrus.

Inhibitory mechanism of opioid binding to receptor by phospholipase A2

1. The inhibition of [3H]naloxone binding to the opioid receptor upon short-term incubation with phospholipase A2 (Plase A2) was abolished by treatment with BSA, but not after long-term incubation. 2. In contrast to the restorative effect of BSA on the strong inhibition occurring with Plase A2, BSA only partially abolished the inhibitory effect of arachidonic acid or lysophosphatides, even though the degree of inhibition was slight. 3. These results suggest that Plase A2 products only become associated with hydrophobic receptor sites or with phospholipids near to the receptor, thus reversibly inhibiting opioid binding, and that irreversible inhibition occurs through release of the phospholipid necessary for receptor binding.

Some properties of brain opioid receptors in membrane bound and solubilized state

In brain membrane preparations, 3H-naloxone binding to bullfrog brain gave the highest values versus other species such as carp, chicken, rat and mouse. Scatchard analysis revealed that the Bmax value of bullfrog brain membranes was three fold greater than that of rat brain membranes. Opioid receptors were solubilized from bullfrog brain membranes using digitonin or 3-(cholamidopropyl)-dimethylammonio-1-propane sulfonate (CHAPS) as the detergent. The properties of solubilized opioid receptors were essentially the same as membrane bound receptors with regard to sensitivity to various treatments. The order of potency for a series of agonists in displacing 3H-naloxone binding in both membrane and solubilized preparations was bremazocine greater than pentazocine greater than morphine greater than delta-receptor peptide. Partial purification of opioid receptors was performed using a fast protein liquid chromatography system. Specific binding activity of 3H-naloxone was increased 10-15 fold within 20 min using the Mono Q column.

Method of Administering Powdered Medicines to Infants: Investigation of Optimal Water Amounts for Achieving a Paste State in Powdered Medicines

A general method of administering powdered medicines to infants is to add a spoonful of water to the powder to make a paste and then making the paste into small dumpling-sized balls. We investigated the optimal amount of water for making a paste for 35 kinds of powdered medicine which included fine granules, granules and dry syrups. The optimal water amount was expressed as an amount per gram of powder. Approximately 80% of the powders examined in this study required 0.2-0.4 mL of water per gram of powder to make a paste that would form small balls. Optimal water amounts were calculated for amounts of powder ranging between 0.1 and 1.5 grams by proportion and when the calculated amounts of water were added, small dumpling sized balls could be formed. In the same way, we also calculated amounts of water required for powdered mixtures of several medicines for 6 prescriptions often prescribed in our pharmacy from corrected standard volumes for each medicine in the mixture. The amounts of water added on this basis achieved the required paste state for all of the powder mixtures used. These results suggest that the optimal water amount for powdered medicines of various weights can be estimated from standard volumes of water by proportion. Thus, optimal water amounts determined by our method may be useful for the administration of mixed powdered medicines to infants.

PROPERTIES OF OPIATE RECEPTOR BINDING IN AN OPIATE TOLERANT STATE

In the mouse vas deferens there was a specific binding site of [3H]D-Ala2, D-Leu5 enkephalin corresponding of a δ-receptor. When mice were injected acutely with opioid alkaloids or implanted with morphine pellets for shorter periods (≦ 2 days), there was an increase in [3H]opioid binding in the brain and the vas deferens. On the other hand, in the brain, longer (≦7days), repeated implantations did not increase [3H]opioid binding 12 hr. after the last implantation.