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PubMed1992

Permeability of brain structures and other peripheral tissues to prostaglandins D2, E2 and F2 alpha in rats.

Parenchymal tissue-uptake (TU) and permeability-surface area (PS) product of [3H]prostaglandins (PG) D2, E2 and F2 alpha [1.85 MBq, 0.5 mg/kg (270 nmol)] were examined in 98 regions of the brain and in 19 other tissues of urethane-anesthetized male rats (180-200 g) 15 sec after i.v. administration with [14C]dextran [0.185 MBq, 0.6 mg/kg (2 nmol)] used as a blood spacer. Slight and insignificant change in blood volume was observed in most of the tissues and brain regions between vehicle- and PG-administered groups. TU for the three PG was markedly high in kidney and lung (2388-3952 ng/g), exceeding the blood concentration (2021-2320 ng/ml), but low (less than 10% of the blood concentration) in epididymis, epididymal fat, testis (59-163 ng/g), brain and spinal cord (33-67 ng/g). TU in brain were detected about 0.1% of the administered PG. Based on a two-compartment model, the PS product for the three PG ranged from 0.75 to 4.16 microliters/g/sec in the latter tissues. The value of brain was 1.22 +/- 0.18 microliters/g/sec for PGD2, 1.69 +/- 0.05 for PGE2 and 1.33 +/- 0.13 for PGF2 alpha, indicating that PGE2 enters the brain more readily than PGD2 and PGF2 alpha. In various brain structures, the ranges of the PS product were large and completely overlapped among the three PG (PGD2, 0.14-1.56 microliters/g/sec; PGE2, 0.05-1.78; PGF2 alpha, 0.05-1.82). The highest PS product for the three PG was found in olfactory bulb and cerebellum (0.96-1.82 microliters/g/sec) and the lowest was in septum (0.05-0.53). However, the level of the PS product was different among the PG in each brain region as follows: PGD2 greater than PGE2, PGF2 alpha in septum and anterior part of pyriform cortex; PGE2 greater than PGD2, PGF2 alpha in olfactory bulb, frontal cortex, basal forebrain, middle part of pyriform cortex, thalamus, hippocampus and lateral neocortex; and PGF2 alpha greater than PGD2, PGE2 in posterior part of pyriform cortex, hypothalamus, amygdala and entorhinal and retrosplenial cortices. Low correlation coefficients (0.708, 0.522 and 0.562 for PGD2, PGE2 and PGF2 alpha, respectively) between the PS product and cerebrovascular volume in various regions revealed heterogeneous cerebrovascular permeabilities of PG.

Animals↗
PubMed1990

Tracer studies of in vivo insulin action and glucose metabolism in individual peripheral tissues.

The ability to study in vivo insulin action in specific muscle types and other individual tissues has been considerably enhanced following adaptation of the euglycemic clamp technique to the rat. The importance of this model derives particularly from its combination with administration of 3H-2-deoxyglucose and 14C-glucose. Analysis of the metabolic fate of these tracers at the conclusion of the clamp enables an assessment to be made of insulin action at both the whole body and the individual tissue level, the latter by estimating a tissue-specific glucose metabolic rate (from 3H-2-deoxyglucose phosphorylation). Information on stored vs utilised glucose can be obtained by simultaneously estimating 14C-glucose incorporation into glycogen and/or lipids. This review briefly considers the basis of the technique and its recent application. It has been used to demonstrate in the rat that in vivo insulin sensitivity differs widely among insulin target tissues, such as adipose tissue, red and white skeletal muscle, and cardiac muscle. The technique has provided a means to study how factors such as diet, exercise, pregnancy, stress hormones and pharmacological agents modify in vivo insulin action in muscle and other tissues, to compare insulin and exercise as stimuli to muscle glucose uptake, and to examine factors which might be important in the aetiology of muscle insulin resistance. These new tracer techniques for in vivo use with the glucose clamp have narrowed the gap that exists between established whole body and cellular in vitro approaches to the study of insulin action and glucose metabolism.

Animals↗