EARLY CHANGES IN PLASMA PANCREATIC POLYPEPTIDE, SOMATOSTATIN, GASTRIN AND MOTILIN LEVELS INDUCED BY H. CONTORTUS INFECTION IN LAMB

HAL Id: hal-00901573

https://hal.archives-ouvertes.fr/hal-00901573

Submitted on 1 Jan 1985

HAL is a multi-disciplinary open access

archive for the deposit and dissemination of

sci-entific research documents, whether they are

pub-lished or not. The documents may come from

teaching and research institutions in France or

abroad, or from public or private research centers.

L’archive ouverte pluridisciplinaire HAL, est

destinée au dépôt et à la diffusion de documents

scientifiques de niveau recherche, publiés ou non,

émanant des établissements d’enseignement et de

recherche français ou étrangers, des laboratoires

publics ou privés.

EARLY CHANGES IN PLASMA PANCREATIC

POLYPEPTIDE, SOMATOSTATIN, GASTRIN AND

MOTILIN LEVELS INDUCED BY H. CONTORTUS

INFECTION IN LAMB

C. Honde, J.A. Chayvialle, J.C. Cuber, Lionel Bueno

To cite this version:

EARLY CHANGES IN PLASMA PANCREATIC

_POLYPEPTIDE,

SOMATOSTATIN,

GASTRIN

AND

MOTILIN LEVELS INDUCED

BY H. CONTORTUS INFECTION IN LAMB

C. HONDE J.A.

CHAYVIALLE

2

J.C.

CUBER

3

L.

BUENO

1

1. Station de

_{Pharmacologie-Toxicologie,}

lNRA, 180 chemin de Tournefeuille, 31300 Toulouse, France. 2. Unité de Recherches de

Physio-Pathologie Digestive,

lNSERM U.45, Hôpital Edouart Herriot, 69734 Lyon Cédex2, France.

3. INRA, Laboratoire de Physiologie de la Nutrition, Jouy-en!losas, France.

Résumé

VARIATIONS

PRÉCOCES

DES TENEURS PLASMATIQUES EN POLYPEPTIDE

PANCRÉATIQUE,

SOMATOSTATINE ET GASTRINE LORS D’INFESTATION PAR H. CONTORTUS CHEZ L’AGNEAU.

-L’évolution des teneurs

plasmatiques

en

polypeptide pancréatique

(PP),

somatostatine

(GH-RIH),

gastrine

et motiline a été

_appréciée

chez

l’agneau

à la suite d’une infestation

expérimentale

orale par 25 000 larves L3 de H. contortus. Ces modifications hormonales ont été

_comparées

à celles obtenues à la suite de l’administration intraveineuse

(IV)

d’extraits

antigéniques

de ces mêmes larves ou de vers

adultes. La

gastrinémie

plasmatique

est

triplée

pendant

la 1&dquo;’heure suivant l’infestation alors que la teneur au GH-RIH est

augmentée significativement

(P

<

0,01)

seulement 180 min

plus

tard et

qu’au-cune modification de la teneur en PP ou de la motilinémie n’est constatée. La somatostatinémie est

également significativement

(P<0,01)

augmentée

60 et 120 min

après l’injection

intraveineuse d’extraits

_{antigéniques}

de larves ou d’adultes et la teneur en PP subit une

_augmentation

tardive 5 à 6 h

après

le traitement. Enfin la

gastrinémie

est

_{également augmentée}

(P < 0,0 1 )

pendant

3-4 h à la suite de l’administration intraveineuse d’extraits

_{antigéniques}

de vers mais non de larves. Ce travail nous per-met de conclure que

l’hypergastrinémie précoce

suivant l’infestation par H. contortus n’est pas la consé-quence d’une

réponse

immunitaire

générale

de l’hôte et est

probablement

liée à la libération

de(s)

substance(s)

par les larves infestantes ou à une _{inflammation locale de la muqueuse; par} contre

l’augmentation plus

tardive de la somatostatinémie semble résulter de

réponses

immunitaires.

Enfin,

les

_changements

des taux hormonaux observés à la suite d’administration d’extraits

_{antigéniques}

peuvent être la

_{conséquence plutôt qu’à l’origine}

des

changements

sécrétoires de l’abomasum.

There is now evidence that some

_parasites

affect the release of

gastro-intestinal

hormones and that in

_{ostertagiasis,}

the hormone concerned alters

_digestive

secretions. In

sheep

fitted with an

isolated fundic

pouch,

infection with 0. circum-cincta larvae was

_accompanied

by

inability

of the

abomasum to maintain its

acidity,

whereas the

pouch

which was

subject

to the same hormonal and neural influences doubled its volume of

secre-tion with an increase of acid and

pepsin

outputs

(Anderson

et al., 1976;

McLeay

et

aL, 1973).

hypergastri-nemia (Anderson et al, 1975) and are abolished

by

surgical

removal of the

pyloric

antrum

_(McLeay

et al.,

19731.

However the occurrence of marked

hypergastrinemia

in abomasal

parasitism,

e.g. H. contortus and 0. circumcincta is not

necessarily

associated with diarrhea which is often present in T. colubriformis infection where

_gastrin

level is not elevated

(Titchen

and Anderson,

1977).

This result

suggests that other hormonal influences may be

implicated

in the

digestive

disorders associated with

parasitism.

Serum

cholecystokinin

(CCK)

levels

apparently

rise after infection with T. colubriformis

_(Dargie,

1979)

and

dogs

infected with Trichinella

_spiralis

show a reduced

pancreatic

secretion in response to

_endogenous

secretin and CCK

presumably

released

by

intraduodenal instil-lation of HCI and fat, but not when these

peptides

are administered

parenterally

(Dembiski

et al.,

19781.

Recently

it has been shown that

changes

in

gastric

acid and other ionic secretions occur

ra-pidly (40-60 min)

after

experimental

infection with H. contortus. These

_{early changes}

_{may be divided} into two parts; a first part

(40-90 min)

which is

reproduced by

placing

into the abomasum a

_bag

containing

exsheathed larvae,

suggesting

that

they

are related to the release of unknown sub-stances into the medium

by

the infective larvae

arriving

into the abomasum

(Buéno

et a/.,

19821;

1

the second _part

(4-6 hours) corresponds

to an

increase in Na+,

HC0

3

-

and CI- concentrations of the abomasal fluid and is

reproduced by

IV ad-ministration of crushed larvae extract, and is attributed to the immune reactions

_during

the larvae

migration

into the abomasum

(Buéno

et al.,

1982).

The choice of these hormones was dictated

by

the

_following

reasons

_{respectively:}

_gastrin

to

assess the

origin

of the

hypergastrinemia

pre-viously

observed (Anderson et al.,

1975),

motilin and

_{pancreatic polypeptide}

for their

_respective

role in the initiation of the

cyclic

pattern of

gastro-intestinal

motility (ltoh

et a/., 1976; Buéno et al.,

1982),

and somatostatin due to the

_ability

of the

synthetic peptide

(tetradecapeptide)

to inhibit

(i)

gastric

secretions

(Konturek

et al.,

1976, 1978)

and

(ii)

the release

and/or

the effects of other GI hormones such as motilin

(Mitznegg

et al.,

1977;

Poitras et al.,

1980).

gastrin

(Konturek

et al.,

1976),

secretin

(Boden

et

a/.,

1975; Konturek

et al.,

1976)

and

pancreatic polypeptide

(Kayas-seh et al.,

1978).

Consequently

the present

experiments

were

performed

to

investigate

the contribution of hormonal factors in the

pathogenesis

of these secretory

changes.

Plasma

gastrin,

motilin,

soma-tostatin

(GH-RIH)

and

_{pancreatic polypeptide}

(PP)

levels were measured

during

6-7 h after

experi-mental infection with H. contortus in lambs and

the variations

_compared

with those observed after intravenous

injection

of larvae and worm

_antigenic

extracts.

Materials and Methods Animals and experimental design

Four 7 to 10 month old lambs

weighing

35 to 40 kg

and raised under parasite-free conditions in concrete

floored pens, in a first series of experiments, and after a

24 h fast, were _orally inoculated with 25000L3 of H. contortus suspended in 0.9 % (w/v) saline solution administered directly into the rumen by the naso-oesophageal route. Samples of blood (5 ml) were taken 5 min before and 20, 40, 60, 90, 180, 240, 300, 360 min after the inoculation. Five days later the sheep were

treated orally with fenbendazole

(10 mg/kg).

Then, in a

second series of experiments

beginning

1 5 days after fenbendazole treatment, antigenic extracts correspond-ing to 25 000 L3 larvae or 25 adult worms were

inject-ed intravenously twice in each animal fasted for 24 h at

5 days intervals. Blood samples were taken just before and 30, 60, 120, 180, 240, 300, 360 and 420 min after

injection. The order of treatment in the 4 lambs was

randomized.

Blood samples were collected into heparinized tubes

containing 1000 U of aprotinin

(Zymofren

ND, Specia,

Paris, France) per ml, immediately centrifuged, and the

plasma was stored deep frozen (&horbar; 40 °C). Samples were analyzed under blind coded conditions and all

measure-ments were done in duplicate. Statistical significance was determined by the Student’s test and analysis of variance.

Antigenic extracts

Antigenic extracts were _prepared from 25 000 3rd stage larvae or adult worms _placed in phosphate buffer (0.05 M) containing NaCl (0.15 M) adjusted to pH 7.8. This suspension was frozen at - 70 °C and crushed (3 to

5 times) until the

morphologic

structures of the larvae

were _destroyed. The suspension was then centrifuged at 15000rpm for 10 minutes and the supernatant was

used as an _antigenic extract. The corresponding amount

of protein injected for larvae and worms was calculated from the dosage of total protein nitrogen according to

Barr et a/. (1975). The larvae (25 000) and worm

(25 adult) antigenic extracts injected corresponded, to

7.1 and 5.8 x 10-4 g of proteins respectively. Peptides assays

Plasma gastrin was measured by radioimmunoassay as _{previously reported (Chayvialle} et a/., 1978).

Antise-rum 28C recognizes equally G17,1 and G14,1 while G34,1 and G17,11 are 40 and 30 °/ respectively as immu-noreactive as G 17,1. Plasma somatostatin was measured with antiserum 56D (Chayvialle et al., 1978; Vaysse et

aL, 1981) that recognizes the 6-1 portion of the

tetra-decapeptide and best binds the immunoreactive

compo-nents at a _slightly acidic pH. Plasma samples were thus acidified to pH 6 with 0.4 M acetic acid immediately

before incubation, and were tested against a standard

Schwartz et al. (1976) using reagents donated _by R.E. Chance. The PP antiserum (Ref.615-105.4-B-248.19)

specifically binds about 40 °/ of the tracer over three

days at a final dilution of 1/1 600000. Bovine PP (Ref.615-D.63-166.7) was labelled with 125 Iodine

(IMS30, Amersham) with lactoperoxydase and was

puri-fied by gel permeation on a 1.5 x 100 cm G50 _superfine

Sephadex column. The same _peptide batch was used for the standard curve. The sensitivity of the assays was

1 pg per ml of incubate. Plasma samples were tested as

100 pl duplicates in a final volume of 1.0 ml. The within-assay and between-assay variations (coefficient of varia-tion, 20 plasma samples) were 7.3 and 9.1 %

respect-ively. Plasma motilin was measured with a newly

develo-ped assay using a _specific rabbit antiserum (Quadra

Logic Tech, Vancouver) at a final dilution of 1/54000,

and porcine motilin (Quadra Logic Tech) as standard and for lactoperoxydase iodination followed by ion-exchange chromatography on a 1 x 10 cm SP-C25 Sephadex

column (Pharmacia). Plasma samples were tested as

100 pl duplicates in a final volume of 1.0 ml. The

sensiti-vity limit was less than _{1 pg per ml} of incubate. The

within-assay and between-assay variations were 5.9 and 11.3 % respectively. All samples were tested in the four assays run in parallel on the same _day. Results were expressed as pg eqv standard peptide per ml plasma.

Results

Hormonal

changes

associated with infection Pancreatic

polypeptide

In 24-h fasted

_sheep

and before infection the immunoreactive

pancreatic polypeptide

(IRPP)

plasma

level was 93+19

pg/ml

(mean ± S.D.,

n

:41,

the individual values

being normally

distribu-ted for the four lambs

(X

2

<

_X

₂

at P >

0.05) ;

in addition intra-individual variations did not exceed 26 %. No

significant

(P > 0.05)

variation of this IRPP level was observed

_during

six hours

follow-ing

the oral administration of 25 000 infective

(3rd

stage)

larvae of H. contortus

(fig.

11.

).

Somatostatin

Plasma levels of G H-Ri

_prior

to infection were

similar for the four lambs

(43

+ 7

pg/mll.

Infection

was followed

by

a

delayed

increase of this level

lasting

2-3 h, the mean maximal level was observ-ed 5 h after infection and

corresponded

to a

69.8 % increase as

compared

to the control value. Gastrin

In fasted lambs the individual

_plasma

levels of immunoreactive

_gastrin

(IRG)

varied from 11 to 45

pg/ml ;

the mean level increased

rapidly

follow-ing

the oral administration of infective larvae, was

maximal

(101 +22

pg/ml)

40 min

_later,

and retur-ned to basal less then two hours later and then

was stable

_during

the

_remaining

_period

of blood

sampling (fig.

1

).

Motilin

Similarly

to

IRPP,

motilin level was unaffected

during

6 h after the infective larvae administration. Effects of

_antigenic

extracts

Pancreatic

polypeptide

There was no

_significant

difference

(P > 0.05)

on the basal level of IRPP between

_days.

Both the

worm and the larvae

_antigenic

extracts

produced

a

late

significant

(P

<

0.05)

increase of

plasma

IRPP level which

_appeared

4-5 h after their intravenous

administration,

this rise was limited to 2 h for larvae extract whereas the IRPP level remained

significantly

(P < 0.05)

increased 7 h after worm

extract

injection

(fig.

2).

At this time the IRPP level reached 890 ± 340

_pg/mi

i.e. a 5.3 fold increase

as

_compared

to the control level. Somatostatin

During

the first hour

following antigen

(worm

and

larvae)

administration the

plasma

IRGH-RIH level increased

_{significantly,}

this effect

_being

slightly

delayed,

less intense and limited to 1 h for larvae extract whereas it lasted four hours with the

worm

antigenic

extract, the

plasma

IRGH-RIH level

_reaching

a

_peak

value of 145 +

38 pg/ml.

Gastrin and motilin

Larvae extract did not affect

_{significantly}

(P > 0.05)

the

plasma

level of

_{gastrin during}

at least 7 h after first

administration;

in contrast,

worm

_antigens

elicited a 100 °/ rise of

gastrin

from 120 to 360 min after their

injection.

The

plasma

motilin level was unaffected

_by

both worm

and larvae

_antigen

administration

_during

the whole

period

of control.

Discussion

In

previous

work we have demonstrated that the abomasal

_permeability

alterations

occurring

rapidly

(0

to 120

min)

after H. contortus infection

were due to a

substance(s)

released

by

the exsheathed larvae

reaching

the abomasum and that these

_{early changes}

were followed

by

immune reactions which were

_{mainly responsible}

of the

gastric

motor disturbances

(Buéno

et

al.,

1982).

The present

experiments

show that

_plasma

gastrin

level was also

significantly

increased

during

the first 60 min of infection i.e. when less than 40 infective larvae are present in the aboma-sal contents

(Dakkak

et al.,

1981)

suggesting

that this hormonal effect may be due to substances released from exsheathed larvae. This

hypothesis

is

supported by

the absence of any

significant

variation of the

_gastrinemia

in the first 60 min after the administration of larvae or worm

antige-ni! extract. On the basis of inhibition of reticulo-ruminal and abomasal

motility

induced

by

penta-gastrin

in

sheep (Ruckebusch, 1971 ;

Onapito

et

in the

_development

of the late motor disturbances. However no inhibition of the reticular and abomaso-intestinal

motility

was observed in the first two hours after H. contortus infection in lamb

(Buéno

et

al., 1982a, b)

but the

hypergastrinemia

observed herein is less marked than that observed several

days

later,

during

the

histotropic

larvae

stage

(Anderson

et

al.,

1975),

which is associated with abomaso-intestinal motor disturbances

(Buéno

et aL,

1982b).

GH-RIH levels were also increased 3-6 h after H. contortus infection in the lambs. A similar but immediate increase was observed after

injection

of worm or larvae extract

_suggesting

that the increase seen after infection was related to immune reactions. However the

antigenic

extracts used herein were _{very crude and could contain} a

lot of non

specific

material

contributing

to this immediate increase in

plasma

GH-RIH level. This increase is moderate and does not

_{significantly}

affect the level of other hormones such as motilin and PP, nevertheless it may be sufficient to contri-bute to the reduction of abomasal H+ secretion which occurs

only

3 to 4 h after infection. This

hypothesis

is in agreement with

previous findings

showing

a rise of the

_gastric

_pH

an increase of

HC0

3

-

secretion 3 to 4 hours after H. contortus infection

(Buéno

et al., 1982

b).

GI hormonal responses observed after

intra-venous

_injection

of worm and larvae extracts with similar

protein

loads were

equivalent

for both PP

and GH-RIH release. However,

only

worm

antigenic

extracts

_{significantly}

increased the

plasma

gastrin

level, whereas motilin level was

unaffected in all cases. Worm extracts increased the abomasal concentrations of

Cl-, Na

+

,

HC0

3

-and the

_{gastric pH during}

about five hours

(Buéno

et al., 1982

b);

the kinetics of

hypergastrinemia

observed herein for a similar duration may be considered as a

physiological

hormonal _secretory response to the

changes

in abomasal

electrolytic

composition. Similarly

the late increase of

pancreatic polypeptide

secretion observed five to

seven hours after

_antigen

administration cannot be

easily explained.

One may

speculate

that it is related either to other hormonal response such as

those of CCK

_(Regan

et al.,

1978)

GIP and VIP

(lverson

et

al., 1978)

or to some

physiological

events such as the

gastric

distension

_by

an increa-sed volume of abomasal contents

(Taylor

et al.,

1978).

Received 6th June, 1984.

Accepted

20th

September,

1984.

Acknowledgements

This work was achieved with skilful assistance of Mrs C. Bernard, G. Bories and Mr G.

Jourdan;

this

study

was

_supported

in part

by INRA,

Depart-ment of Animal

_Pathology.

Summary

Plasma levels of

pancreatic polypeptide

(PPI,

somatostatin

(GH-RIH1,

gastrin

and motilin were measured

during

6-7 h after oral infection with 25 000 infective

(3rd

stage)

larvae of H. contortus in lambs or after intravenous

injection

of larvae or worm

antigenic

(Ag)

extracts. A 3-fold increase in

plasma gastrin

was

observed

_during

the first 60 min after infection and GH-RIH increased

significantly

(P < 0.01)

180 min later whereas both PP and motilin remained

unchanged.

An

early

(60

to 120

min)

increase in GH-RIH H and a late

(5

to 7

h)

increase in PP

plasma

levels were observed after both worm and larvae

_antigenic

extracts whereas

_plasma

motilin was unaffected. Plasma

gastrin

was

_{significantly}

(P

<

0.011

increased

during

3-4 h

following

the

injection

of worm but not of larvae

antigenic

extract. It was concluded that

the immediate

hypergastrinemia

following

H. contortus infection is not the consequence of a

_general

immune response of the host and is

probably

related to the release of unknown

substance(s) by

the infective larvae into the abomasum or to mucosal inflammation due to a local immune response; in contrast, the increase in

plasma

GH-RIH levels

appeared

to be the result of

_antigenic

reactions. The other hormonal

_changes

observed after

Ag

injections

may be the consequence rather than the reason of

changes

in abomasal _{secretory pattern.}

References

ANDERSON N., BLAKE R., TITCHEN D.A., 1976. Effects of a series of infections of Ostertagia circumcincta on

_gastric

secretion of sheep. Parasitology, 72, 1-12.

ANDERSON N., HANDKY J., TITCHEN D.A., 1975. Hypergastrinemia during a

_{parasitic gastritis}

in sheep.J. Physiol.,

256, 51-52.

BARR G.W., BARTLEY E.E., MEYER R.A., 1975. Feed Processing. 8. Estimating microbial protein in rumen fluid with

precipitating agents of incubated mixtures of uncooked grain plus urea or starea with differential centrifugation.

BODEN G., SIVITZ M.C., OWEN O.E., ESSA-KOUMAR N., LANDOR J.H., 1975. Somatostatin suppresses secretin and _pancreatic exocrine secretion. Science, 190, 163-164.

BUENO L., DAKKAK A., FIORAMONTI J., 1982 a. Gastro-duodenal motor and transit disturbances associated with H. contortus infection in sheep. Parasitology. 84, 367-374.

BUENO L., FIORAMONTI J., RAYNER V., RUCKEBUSCH Y., 1982 h. Effects of motilin, somatostatin and pancreatic polypeptide on the migrating myoelectric complex in pig and dog. Gastroenterology, 82, 1395-1402. BUENO L, HONDE C., LUFFAU G., FIORAMONTI J., 1982 c.

_Origin

of the early digestive disturbances induced by

Haemonchus contortus infection in lambs. Am. J. Vet. Res., 43, 1194-1199.

CHAYVIALLE J.A., DESCOS F., BERNARD C., MARTIN A., BARBE C., PARTENSKY C., 1978. Somatostatin in

mucosa of stomach and duodenum in _{gastroduodenal} disease. Gastroenterology, 75, 13-19.

CHAYVIALLE J.A., MIYATA M., RAIFORD P.L., THOMPSON J.C., 1980. Effects of test-meal, intragastric nutrients, and intraduodenal bile on plasma concentrations of immunoreactive somatostatin and vasoactive intestinal

peptide in dogs. Gastroenterology, 79, 844-852.

DAKKAK A., FIORAMONTI J., BUENO L., 1981. Haemonchus contortus third stage larvae in sheep: kinetics of arrival into the abomasum and transformation during rumino-omasal transit. Res. Vet. Sc., 31, 384-385. DARGIE J.D., 1979. The

_{pathophysiological}

effects of

_{gastrointestinal}

and liver parasites in sheep. /n: Y. Ruckebusch,

P. Thivend (eds.), Digestive physiulogy and metabolism in ruminants, 349-371, MTP Press.

DEMBISKI A.B., JOHNSON L.R., CASTRO G.A., 1978. Altered release of gastrointestinal hormones as a component in the pathogenicity of _{parasites. Proceedings} of the 4th lnternational

Congress

of Parasitology, Section F, 1 5, Warsaw.

ITOH Z., AIZAWA I., TAKEUCHI S., COUCH F.C., 1976.

_Hunger

contractions and motilin in _{G. Vantrappen} led.)

Proceedings of the Fifth International Symposium on Gastrointestinal Motility. Herentals, 48-55, Typoff-Press.

IVERSON J., BLOOM S.R., ADRIAN T.E., HERMANSEN K., 1978. Control of glucagon, insulin and pancreatic poly-peptide secretion in the isolated pancreas. Acta Endocrinol. (suppl.), 212, 8.

KAYASSEH L., HAECHI W.H., GYR K., STADLER G.A., RITTMAN W.W., HALTER F., GIRARD J., 1978. The endoge-nous release of pancreatic polypeptide by acid and meal in dogs. Scand. J. Gastroenterol., 13, 385-391. KONTUREK S.J., SWIZERCZEK J., KWIECIEN _N., MIKOS E., OLESKY J., WIERZBICKI Z., 1978. Effect of

somatosta-tin on meal-induced _gastric secretion in duodenal ulcer patients. Am. J. _Dig. Dis., 22, 981-989.

KONTUREK S.J., TASLER J., CIESZKOWSKI M., COY D.H., SCHALLY A.V., 1976. Effect of growth hormone

release-inhibiting hormone on _{gastric secretion,} mucosal blood flow and serum _{gastrin. Gastroenterology,} 70, 737-741. KONTUREK S.J., TASLER J., OBTULOWICZ W., COY D.H., SCHALLY A.V.,1976. Effect of

growth

hormone-release

inhibiting hormone on hormones stimulating exocrine pancreatic secretion. J. Clin. Invest., 58, 1-6. McLEAY L.M., ANDERSON N., BINGLEY J.B., TITCHEN D.A.,1973. Effects on abomasal function of Ostertagia

circumcincta infection in sheep. Parasitology, 66, 241-257.

MITZNEGG P., BLOOM S.R., DOMSCHKE W., DOMSCHKE S., WUENSCH E., DEMLING L., 1977. Pharmcokinetics of motilin in man.

_{Gastroenterology,}

_{72, 413-416.}

ONAPITO S.J., DONAWICK W.J., MERRITT A.M., 1978. Effect of gastrin on emptying and composition of digesta of the omasum of _sheep. Am. J. Vet. Res., 39, 1455-1458.

POITRAS P., STEINBACH J.H., VAN DEVENTER G., CODE C.F., WALSH J.H., 1980. Motilin-independant ectopic

fronts of the _{interdigestive myoelectric complex} in dogs. Am. J. Physiol., 239, G215-G220.

REGAN P.T., GO V.L.M., DIMAGNO E.P.,1978. Human exocrine pancreatic secretion and pancreatic polypeptide

response of CCK on octapeptide of CCK. American Pancreatic Association, Annual Meeting, Nov. 2-3, Chicago,

Abstr. 46.

RUCKEBUSCH Y., 1971. The effect of pentagastrin on the motility of ruminant stomach. Experientia, 27, 1185-1186.

SCHWARTZ T.W., REHFELD J.F., STADIL F., LARSSON L.K., CHANCE R.E., MOON N., 1976. Pancreatic polypeptide

response to food in duodenal ulcer patients before and after _{vagotomy. Lancet, 1,} 1102-1105.

TAYLOR I.L, FELDMAN D.M., RICHARDSON C.T., WALSH J.H., 1978. Gastric and cephalic stimulation of human

pancreatic polypeptide release.

Gastroenterology,

75, 432-437.

TITCHEN D.A., ANDERSON N., 1977. Aspects of the

physio-pathology

of parasitic

gastritis

in the sheep. Aust. Vet. J., 53, 369-373.

VAYSSE N. CHAYVIALLE J.A., PRADAYROL L., ESTEVE J.P., SUSINI C., LAPUELLE J., DESCOS F., RIBET A., 1981. 1 . Somatostatin-28: comparison with somatostatin-14 for plasma kinetics and low-dose effects on the exocrine