tium-90 had no untoward effccts on growth or general well-being of the animals. How- ever, the quantitative changes reported milk product.

mould have to be taken into copsideration if dicts were ever to lw formulated wing this

THIRST mu RATS RESULTING FROM mIpovoLEMu AM) HYPEROSMOLARITY

Regulation of hotly water, both iatahc and excmtion, is at least partly medinted by the hypothalamus. For an exainlc. it has been shown in several species that lesions in the lateral area8 of the hypothai- amus m l t in adipsia. This is evidence that specialired h y p t halamic osmorecep- tom function in eliciting thirst. E. M. Stricker (Am. J . P h y d . 211,tSt ( I = , ) haa shown that oeiiiorcceptor expansion alone docs not elicit thirst, and that cellular volume changes are not necessary to elicit thirst. He concluded that iniportant etim-. ulants of thirst are osmoremptorn rcspon- sive only to an increased effective osmotic pressure of the extkcellular fluid, and vol- ume receptors responsive to decreased in- travascular fluid volume.

Stricker and G. Wolf (Php'ol. Behau. 2, 33 tl#7'1) have, in tlirec experiments, de- termined the effect of water and imtonic d i n e preloads on the subsequent watvr or d i n e intake of rats treated with hyper- omnotic colloid (plyethylene glycol) or hypertonic saiinc.

The hypertonic saline injection causes an elevation of the osmolarity of extracc*llular fluid, cellular dehydration, and, as a m d t of antidiuretic hornlone release, formation of a highly concentrated urine. The p l y - ethylene glycol injection causes a neques- tration of extracellular fluid 4 localized edema) and results in no loss of cell water, but the d w m d M d \-olunic multr in renal retention of both watcr and mlium. Thus the two injections affect the two pro- powxi t w of nvcptor* indcpcndrntly.

- - - - - Adult male rats kept in nictubolim cagtw

were depriwd of food and water from 9:OO a.m. to 5:oO pm. ench day. Water intake was measured daily between 5:oO and 6:O p.m. in fiw+rninutm increments. "he rats had access to food and water from 6:OO pm. until 9:OO am.

At initiation of the eighth deprivation period, the rats were injcctcd subwtan- eoudy witb 5.0 ml. of 1.0 molar liodiurn chloride or 5.0 ml. of 10 per cent plyethyl- cne glycol (PEG) in 0.15 molar sodium chloride. At 4:OO pm.. preriML.rly injected ratp were given no preload or given 15 ml. of either water or 0.15 molar d i u m c b b ride ria a lrtornaeh tuhe. At 5:a) p.m. water intake was detcrniined. a* during the pre- experiinental priod. r r ine rae collcctd during the depriration priod and analyzed for mdium.

In the first experiment, during a rcpeti- tion of the above trratmcnt, bloocf Ranipler from a group of the mu WCR taken when water intake was normally measured. The blood wan analyzed for plasma mmolarity, plasma pmtein mncentration, and b e m a b crit. The 1.0 molar wiiuni chloridc injection

c a u d a dcefinitc natriumis: dmut 4 3 riiEq of d i u m were cxrrctcci during thc seven hours folloking the S niEq injection. The urinc sf those rat* rccciring t h PFA; injtrtion had nlmut orw-t hird of thrir nor- mal conccntration of sodium and t h total volunw ; thwcfore rrlatively littlc Irocliura was cYtcn4ed.

Tlmw rats injcctnl with a hyprtonic

.4ugust ftm] II?BITIOH IlEvIcIpil 247

d i n e solution and either not preloodcd or proloadd with isotonic d i n e wffcrcd from ineread plasma osrnolaritj., ahereas those receiving a water preload had a plamial molarity bclow nornial. PEG injections caused 'deerpmd plasma volumes, hut thie modition was correctcd by prcloading with 0.15 molar d i u m chloride.

The water intake of t h rats m i v i n g PEG and prolondcd with 0.15 molar Fodiuiii chloride was much less than thocu! eimilnrly trmted but receiving eitbcr no preload or water 4 1.5 versus 6.0 nil, p < 0.01 b. The rats injected with 1.0 niolar d u r n chloride and preload4 with water drank much lese than those rrreiving eitbcr no prcload or 0.15 molar d i u m chloride (28 versus 8.0 nil., p < 0.01 1.

Even though thc thirst that follows PEG injections in tcrnis of water coiirurwd is similar to that which follows tlw 1.0 molar d i u m chloride, I d y fluid composition and distribution arc quite dificrcnt. Without a change in ostaolarity. PEG injections cause a 15 to 20 p r wnt d w m in plasnm vol- ume, which hau twrm rho- to be sufficient to induce thirst (31. 1. Grcgcm, in Jlec- I ~ . d u Phyuiologp in Jltdprn Jfcdicinc. P. Uard. Editor, S i n t h Edition. p . -1075. Yocrbg. St. Lnricr. 1941 b. In contrast, the authors calculatcd that approximrtcly S.5 p r rent crhrinkapc in intrncclhlar volunrc. multed from thc d i u m chloride injcction which is grcater than thr 1 to 2 p r rent de- C~('HI(C that A. V. Wolf (An. J. Phymkl. 161. 76 (1@50)) found to he II stimulus thrcrrhold for drinking and that E. B. Vernry (Proc. Rou. Sor. R 1 s 2S ( 1941, b found to lw a atiniulua thrt.r;hold f o r anti- diunat ic hornionc crcrction.

The hody fluid conccnt rat ion and volume ' of the rata injected with PEG rcturncd to

nearly noniirl after pwlonding with 0.15 molar sodium chloride. and the rats drank wry lit t Ic watcr. Siniilwly, prclording with waiter thc rats injected with 1.0 molar so- dium chloride. mwltcd in a below normal. i r i a t c d of rr high, plnsnra mnrolarity, and the* rats lost much of tlwir thirst. Prcloading

0

tlre rats injected with PEG with water, al- though causing a below nornial osmolarity, did not alleviate the decreased body fluid volunle, and the rats remained thirsty. Also tlw rats injected with d i u m chloride and prcloaded with isotonic saline etill suffered from an elevated plasma oemolarity and thus =ere thirsty.

Strieker and Wolf suggest that t& eep- aratc- systems function in water balance reg- ulntion. An m o r e p l a t o r wntw changea in the effective osmotic pmaure of the extra- wllular fluid, and a volume regulator senses e h u n p in intraccllulrr fluid volume. Each is c:ipMc of effecting water consewation and conditions of dehydration by stirnu- lntingboth thirst and antidiumir.

A Fecond expcrimcnt tested whether rate suflcring the same types of thirst i n d u d in

* the first would wlwt cithcr 0.15 niolar w- diunr chloride or water to drink. The cx- Irrinwntal pnmdurc was the same as that

-ef Exprinwnt I, except tliut both imtoeic sdiw and water were available to the rat t h i n g thc hour drinking test.

Aftcr Pffi injections the rats drank eig- nificantly niorc salitw then water, but there was not a definite pmfcrcnce for cithcr mlutioo folloming either type of injection. The authors, in an attcnipt to increase the Imlrahility of inducing a differenw in sa- line prefemncr In-trwn the two types of t l i i ~ . did a third cxprinient. The experi- nicmtrl prorcdurc was the same as that of . FApxinient I1 exrrpt that 20 instead of 10 1n.r miit PEG was injectd. In this caw, tlit. total intake of fluid was greater than that of rats injected with 10 per cent PEG in Eqwrinrent XI. In tliie experiment the rats nianifrwtcd a slight saline preference undc-r both conditions. but tliers was no &fit-rcncc in saline prcbferriicc Irtwwn the two conditions.

Stricker and Wolf dipcuss wvernl poe- sible explanations of why the second and third experiments did not clearly dcmon- strate a fluid prcfcrcnce predicted by thc m u l t s of Experiment I. Perhaps the nrwt

248 h ’ t ~ r r I O W

important reason would be palatability of the solution. A 0.15 per cent sodium chloride aolution is knom to be inore palatable than water (E. R. Christensen, J. Comp. Pliyuiol. P a p d d . SS, S.97 (IS4321 1. This preference u d d have ha& a greater influen& on drink- ing behavior than a delayed response of a eolution more eficient in Batiating a thiret. Perhaps rab suffering from “hyporokmic thirst” would have selected moreemmen- trated saline than those rats suffering from 4 ‘ h y p c ~ ~ l a r thirst” if tbe gradient of test solutions had been greater. Ae Stricker and Wolf have previously

shown ( J . Comp. Phyaiol. Pauchd. 62, f l 5 (IsSrr) 1, hypo\.oleniia is an important fac- tor, although not sufficient in itself, in causing a sodium appetite as well as thirst.

.. REVIEWS [I’d. M. No. 8

It is not clear, though, whether tbeec drivm (sodium appetite and thirst) which IVP t~oniewhat depcndcnt on hypovoleinin, arc i n d i n t 4 by the same receptor, nrotiva- tional, and satiation systcnir.

These experiments show that intragnstric prcloada of isotonic saline d u a “hypo- voleniic t tiiwt” mom effectively than pre- ?&dr of water, and that prclosde of water reduce ‘.l+-~wmmolar thirst” more e l k - tivcly than preloads of h t o n i c MI~IW. In other tests, though, rats did not clearly select the solution than would molh effec- tively alleviate their particular thirut. T h m data ruppoort the hypothesis that there am receptors wnsing both voluiire and osmo- larity of the intrarmular fluid which func- tion in bod+ muter regulation.

Biz TRA!!SPORT IN RED CELL MEMBRANES

Phpbl& u p t a k e 4 B,. by red cell membmrra u by odnrrption to the rtnrma oj the ell. rrquiring aenm prokin, d c i u m . and moqnmm’um. Yvtahulie inhibiton &D

nof d e c f f h u rractwm.

. Cell permeability of the largest and m& complicated vitamin, Blr, has attracted much interest in gastrointestinal physiol- ogy. This hrge moleeule (molecular weight 1,500) cannot, in physiologic concentrations, diffue acmm the intestinal membrane by iteelf. Blt requires an even larger molecult+ gastric intrinsic factor (m.w. 5O,ooO)-for absorption. E v a then, interaction between tbeee two compounds does not insure ab- sorption. Tbe mucus membrane of tbe ileum (in many different species, including man) is also r e q u i d .

This peculiar and fascinating mechanism hse atimulated considerable research in membrane kinetics. Although no direct pmof e x i d , most studies suggest that Bar intrinsic factor complex entere the mucosal cell during transport (Sulrition RetGwa 23, 33 ( 1 S 6 ) ) . Data pertaining to uptake by times other than tbe gut have also demonstrated the need for thie large mole- a l e to be bound to mme protein compound for transmembrane movement. For indance,

partial maturation of niegaloblawtr ( in vitro) can be stimulated by Blt only when serum or gastric juice k present (S. T. Callcnder and L. C. Lajtha, Blood 6, Zw (1961)). Some type of protein interaction must occur during transcellular tramport. Other data, (LB well, have shown that B13 uptake by t k u e ‘requires protein binding. To investigate further the mechanism of

vitamin Bat uptake by tissue, F. P. Retief, C. W. Gottlieb, and V. Herbert studied B I ~ uptake by erythrocytes ( J . Clin. Inuut. 45, IlW7 (Ilpes) 1. Since previous reporb have suggested that mature red blood rplle do not take up significant aniounta of vitamin BIZ

compared with blood with a rising reticu- loryte count, two cell prepm&ons were used: blood rich in mticulwytes q d nonaal blood. Reticulocyte-rich blood vm otltrrincd from patients with hcnrolytic disease or iron deficiency anemia rwponding to trent- ment.

Cells were unshed and suspnded in a edution of calcium and sodium chloride.