The vagus, motilin, and the migrating motor complex

1912

CORRESPONDENCE

this technique similar

GASTROENTEROLOGY Vol. 107, No. 6

has advantages

over current

alternatives

that provide

information?

the smooth

muscle

significantly

lower quantities

sphincters

cent nonsphincteric

E. E. DANIEL

The studies

Department of Biomedical Sciences

comparing

Faculty of Health Sciences

motility

We appreciate

SUSHANTA

tinal polypeptide gene expression is characteristically higher in opossum gastrointestinal sphincters. Gastroenterology 1994; 106:1467-1476.

Reply.

The issue raised by Dr. Daniel

studies

using

important study

molecular

to keep in mind

of VIP mRNA

the neuropeptide bodies.

biology

transcripts,

but

disorders

are transported

try usually

requires

nocytochemical reason

studies

there

tent.

RIA

will

in these

simply

content

without

any relationship

problem

of antibody

The present

recognition

studies

muscle sphincteric importance concerns

would

to the tissue

definitely

The main message transcripts

apply

VIP mRNA

transcripts

it is clear (Figure the myenteric

the differences

to minimize

the

approaches.

The

out

The Vagus, Motilin, Motor Complex Dear Sir: In a recent paper, Yamamoto cation

at pH

the intact

1 inhibits

dog stomach

not in the extrinsically

by Dr.

the VIP mRNA

reflex whereby

denervated

fibers would neurons

vagal efferent

inhibit

We would like to suggest

We would

sensory

arising

information

continued

bowel migrating

tissues.

To pinpoint

the

ance ofphase

to compare

the

is, with

muscle

is coming

cells, suggesting

transcripts

in smooth

from

may not be ex-

muscle

mass of two

differences

in VIP

cycling

III-like

gastric

activity

acidification,

with vagal blockade small

bowel

efferent ticularly

phase

(absent

vagal pathways

cells of Cajal,

excitation)

ance of gastric Cal3 and/or

in sphincteric actin

vs. nonsphincteric

tis-

is a novel idea but may not be

our recent

studies2

increases

acidification,

types of cells is not known. muscle

blockade

have shown

that

of inhibitory

more

tonic,

probably

into play with chronic Whether inhibition

in response

to mot&n is identical

acidification

reflects

injections.2

That shown

phase III with persistence

of the

blockade

neither

afferent

Thus, vagal integrity whether other

responds

such

is cycli-

as a cyclical

this activity.4X’ The fact to the motilin

and is not influenced the adaptive

nor

(and par-

for the normal appearthis excitation

factors

levels to produce pouch

the small the appear-

to that

vagal

allowing

to

phase III activity

the picture

activity

of vagal input,

is primarily

of the vagal nerves

levels with

appears to be a prerequisite

phase III-like

that in our view

gastric

mot&n

are operative.

in the absence

of interstitial

activation

(MMC) but also prevents

gastric

III). With

the differences.

the contribution

to the low pH

acidification

Cooling

motor complex

gastric

Interestingly,

from gastric

of plasma

types of cells. From our studies’

propose

that the effect of the vagal

the spontaneous

that the message

in but

these vagal efferent

explanation

propose

turn off vagal efferent excitation.

motilin

sues based on smooth

through

an alternate

is even more likely.

in plasma

always practical.

fibers responding

the stomach

pouch

is a long vagovagal

fibers. Presumably

in dogs not only abolishes

than

gastric

pouch.’ The authors

despite

there were no apparent

the VIP content

gastric

acidifi-

activity

in the stomach.

that the denervated

To compare

innervated

vs. nonsphincteric)

in all the sphincteric

III-like

for this inhibition

vagal sensory afferent

in turn activate

phase

and the vagally

mRNA levels in the tissues with or without mucosa, suggesting a minimal contribution of submucosal neurons and the mucosa toward blood vessels, and other

et al. showed that intragastric

motilin-induced

show that the levels

in the VIP mRNA

However,

and the Migrating

(sphincteric

and not the smooth

Likewise,

Street

The studies muscle

in different

Waht

1025

Philadelphia, Pennsylvania 19107

it will be important

smooth

on the basis of the differences

types of tissues.

they

tract for VIP mRNA

as pointed

higher

6 in our paper)

neurons

Thomas Jeffwson University

that the most likely explanation

levels.

to RIA and immunocytochemistry.

were reproducibly

nonsphincteric

of the neuro-

new because

was never

composition

of tissues

basis for the differences,

in the tissues

to scan all smooth

of the study’ was to compare

in two types

the adjacent

that

and

investigations

the

origin

Then there is a

and breakdown

important

of the tissue composition.

of VIP mRNA

plained

neurons.

in the neuropeptide

of the study

con-

without

extrinsic

of the RIA and immunocytochemistry related

regardless

of the peptide

regions of the gastrointestinal

The purpose

immunocyto-

by the VIP variants

are both

for this

of the peptide

of unknown

These limitations

results.

VIP RIA may include

to the intramural

the first comprehensive

expression.

cellular

Therefore,

may lead to wide variations

constitute

In addition,

the presence

M.D.

D.V.M.

tinal polypeptide gene expression is characteristically higher in opossum gastrointestinal sphincters. Gastroenterology 1994; 106:1467-1476. 2. Liddell RA, Chakder S, Rattan S, McHugh K. Differential isoactin gene expression in the sphincteric and nonsphincteric gastrointestinal smooth muscles of the opossum. Proc Sot Exp Biol Med 1994;205:321-326.

the

for immu-

Perhaps

PH.D. PH.D.

on the neuropeptide

quantitation

of the nerve terminals

investigation.

peptide

Daniel

show

variable

difficult

thickness.

regions.

provide

the site of its origin.

peptide

under

of their

lack of information

does not readily

revealing

with

and

addressed.

1. Bandyopadhyay A, Chakder S, Lynn RB, Rattan S. Vasoactive intes-

the synthesis,

are notoriously

because

is a relative

immunocytochemistry chemistry

pretreatment,

VIP neuro-

cell

down the axon to the nerve terminal.

regions

affecting

raised by Dr. Daniel

are im-

of the cell bodies, immunocytochemis-

colchicine

the sphincteric

for

tissues in the

Division of Gastroenterologyand Hepatolog3i

is to be able to examine

Following

B. LYNN,

groundwork

Department of Medicine

In the

level in the neuronal

limitations.

for the visualization

Moreover,

the merit

RICHARD

It is

(RIA) and immunocytochemistry

have certain

neuropeptides Therefore,

approaches.

CHAKDER,

SATISH RATTAN,

to most of the

newer

of each approach.

at the transcriptional

Radioimmunoassay

portant

is applicable

and other

the strengths

important

the questions

ALOK BANDYOPADHYAY,

1. Bandyopadhyay A, Chakder S, Lynn RB, Rattan S. Vasoactive intes-

express

than the adja-

gastrointestinal

hope that these have been appropriately

Hamibon, Ontario, Canada L8N 325

tract

mRNA

tissues.

provide

in different

of certain

transmission.

1200 Main Street West

muscle

above

the VIP mRNA

pathophysiology

McMaster University

smooth

discussed

of the gastrointestinal of total isoactin

injection

by the gastric

mechanisms

that

come

denervation.* of the stomach

of the stomach

through

can induce

sympathetic

active adrenergic pathways

was not

December 1994

studied

CORRESPONDENCE

in the paper

is mentioned

by Yamamoto

in the abstract

is also less likely.

With

et al., although

summary.

and motilin

injections

in the presence

vagal blockade,

absence

personal

do not produce

of pharmacological

this possibility

We suspect

phase III of the MMC is not due to unopposed

this mechanism

phase

Dear Sir:

of the spontaneous

adrenergic

adrenergic

Lieverse et al. report that in human

inhibition6

III-like

activity

blockade

(unpublished

even

3.

4.

5.

6.

of cholecystokinin plasma ings,

observations).

of Phase III activity by acidifying stomach in vagally denervated and innervated dogs with gastric pouches. Gastroenterology 1994; 106:1533-1541. Hall KE, Greenberg GR, El-Sharkawy TY, Diamant NE. Relationship between porcine motilin-induced migrating motor complex-like activity, vagal integrity, and endogenoug motilin release in dogs. Gastroenterology 1984;87:76-85. Miolan JP, Roman C. Discharge of efferent vagal fibers supplying gastric antrum: indirect study by nerve suture technique. Am J Physiol 1978;235:E366-E373. Andrews PLR, Bingham S. Adaptation of the mechanisms controlling gastric motility following chronic vagotomy in the ferret. Exp Physiol 1990:75:811-825. Grundy D, Hutson D, Scratcherd T. A permissive role for the vagus nerves in the genesis of antrc-antral reflexes in the anaesthetized ferret. J Physiol 1986;381:377-384. Chung SA, Valdez DT, Diamant NE. Adrenergic blockade does not restore the canine gastric migrating motor complex during vagal blockade. Gastroenterology 1992; 103:1491-1497.

concentrations,

dance

with

conclusions

McLaughlin Pavihon

Toronto, Ontario MST 2S8, Camah

very much the comments

et al., and we basically

agree with

that the effect of the vagal sensory acidification paper,

is primarily

however,

the stomach

the mechanism stomach

activation

by which

through

the present from gastric

study

elucidated

from gastric

that

the vagally indicate

neurons

induces

phase

in the stomach.

decreases

feeding

decrease

Furthermore,

in food intake

is in accor-

The results

to those of their with

saline infusion.

subjective

criteria

such as desire to eat, hunger

fullness, and prospective

feeding

intentions

Lieverse

et al. conclude

in this former

CCK-33

to plasma

meal does not have a major hunger recent

feelings.” paper

unclear

They

“.

effect on food intake findings

infusion

of

after a fatty

and postprandial

in the discussion

of their

and conclusions

which

are

to us.

Our own studies

support

a role for endogenous

satiety.3 We have also given a CCK-8 dial plasma intake

that

to those observed

do not comment

on these different

feelings,

were not affected by CCK.

study

levels comparable

and

previous

did not produce

CCK-33

compared

feel-

compared

thar “This finding

work in which the same dose of intravenous a significant

in hunger

intentions

effect of CCK.”

are in contrast

infusion

physiological

concentrations

compared

infusion

CCK in control

to reproduce

and shown a significant

of

postpran-

reduction

in food

with saline infusion4

A. B. BALLINGER M. L. CLARK

cholinergic

that activation

pathway. of sensory

that

similar

and that this problem

of motilin’s

action

action

in the is finally

Our findings neurons

in

arising

to turn off the vagal efferent excita-

on the pathway

are identical

us.

that includes

the mechanism

findings,

cannot

the vagova-

by which

antral

be substantially

only because

Lieverse RJ, Jansen JBMJ, Masclee AM, Lamers CBHW. Satiety effects of cholecystokinin in humans. Gastroenterology 1994; 106:1451-1454. Lieverse RJ, Jansen JBMJ, Zwan A vd, Samson L, Masclee AAM, Lamers CBHW. Effects of a physiological dose of cholecystokinin on food intake and postprandial satiation in man. Regul Pept 1993; 43:83-89. Ballinger AB, Clark ML. L-Phenylalanine releases cholecystokinin and is associated with reduced food intake in humans: Evidence for a physiological role of CCK in control of eating. Metabolism 1994;43:735-738. Ballinger AB, McLaughlin L, Medbak S, Clark ML. Cholecystokinin is a satiety hormone at physiological postprandial concentrations. Gut 1993; 34:AlOl.

the pictures

is closely related to the mechanism

Reply.

The regulation

of appetite

control

is complex.

in animals,

regulation

Like Drs. Ballinger

and Clark, we are interested

in the regulation

of food

in humans.

in the role of CCK The recent allowing

development

measurement

and the availability

We have studied plasma

in fasting

subjects,’

Gastrointestinal Research Laboratory

CCK on satiety

Gunma University

decreases

Maebashi, Japan

intentions

CCK-receptor

control

antagonists

delineating

in humans.

subjects.i

of CCK that produced

satiety

we have studied

feelings,

have enabled

the physiological

on preprandial

and on postprandial

after stimulation

in fasting

its

in both lean and obese subjects.

concentrations

in this journal,

in hunger

intake

about

and specific radioimmunoassays

the effect of an infusion

meal.’ In addition

As reported

is known

of the low plasma CCK levels in human plasma of potent

role of CCK in appetite

a preload

of sensitive

a series of experiments

us to perform

physiological

and very little

Most studies

have been performed

0. YAMAMOTO 2. ITOH Institute of Endominology

7BE, England

At present,

III activity

that motilin’s

blocks phase III in the stomach by comparing

In our

fibers inhibit

draw such a conclusion.

appears

We believe

excitation.

these vagal

of inhibitory

motilin

somewhere

gal reflex center. acidification

arising

but it is certain

acidification

tion by motilin

explanation

information

et al. seem to have misunderstood

we cannot

is not known,

mediated

alternate

to turn off vagal efferent

Drs. Diamant

From our experiment

made by Drs. Dia-

their

we did not propose

through

In this respect,

satiety

of this study

London EClA

3 99 Bathurst Street

We appreciate

significant

They conclude

a physiological

produced

Department of Gastroenterology

Toronto Hospital (Wartern Division)

Reply.

induced

an intravenous

which

St. Bartbo/omew’s Hospital

Gastrointestinal Motility Research Laboratory

mant

subjects

(CCK-33),

the wish to eat, and prospective

N. E. DIAMANT S. A. CHUNG K. E. HALL

12-419

33

with saline infusion.’

1. Yamamoto 0, Matsunaga Y, Haga N, Mizumoto A, ltoh Z. Inhibition

2.

1913

with

satiety parameters without,*

intraduodenal

the infusion

and with

the effect of endogenous fat.*

of CCK induced

significant

the wish to eat, and prospective No clear differences

between

feeding lean an