Gastric antisecretory effect of sauvagine in rats: Possible mechanisms

Pharmacological

Research,

Vol. 22, Supplement

13

I, 1990

GASTRICANTISECRETORY EFFECTOF SAUVAGINEm RATS: POSSIBLEMEW.ANISMs. Giovanna IMPROTAand Maria BROCCARDO Institute

of Pharmacology III

Key words: gastric

output,

- University

sauvagine,

%a Sapienzall.

adrenergic

Rome, Italy

systems.

INTRODUCTION Sauvagine (SV) is a peptide

isolated

from the skin

frog Phyllomedusa sauvagei and structurally SV and CRF elicited

a number of similar

se of plasma catecholamines, and the inhibitian (2).

of food intake,

The dose-related

inhibitory

(GAS) in rats has been well or histamine

receptors,

The peptide

D-glucose

biological

stimuli

gastric action

responses:

concentrations

(vagal)

tihibiting

acid output

acid secretion

and is not mediated

the highest

the increa-

emptying and gastric

of SV on gastric

established

as pylorus

to mammalian CRF (1).

ACTH and 4 -endorphin

but by a cholinergic

shows, in fact,

vagus-dependent

glucose,

related

of the South American

through

secretory

pathway(s).

potency against

ligation,gastric

opioid

distension,

such

%-deoxy-

and bethanechol.

It has been shown that

release

gic system reduce the vagally we have investigated adrenalectomized of adrenergic

stimulated

the ability

rats

study,

with different

prazosin/PRZ,

in order to ascertain

types

biosynthe-

the role

in the gastric

GAS in

yohimbine/

or with a prostaglandin

system and prostaglandin-mediation

in 2-h pylorus-ligated

of adrener-

(SC) SV to inhibit

pretreated

agents (phentolamine/PHE,

sis inhibitor
of subcutaneous

haloperidol/HLP)

and activation

GAS. Thus, in the present

(ADR-X) and in rats

blocking

YOH, propranolol/PRP,

of prostaglandin

of the sym-

response to SV

rats.

RESULTS SC) decreased GASby 83% in conscious

SV (2.5 p&g, (52.7 ,W); ted rats rats

(213.0

(109.0

treated

adrenalectomy,

rats

SV-treated

pEq),

PEq). rats.

which did not modify acid output

halved the reduction

WE (4 mg/kg, ip)

and further

pylorus-ligated

significantly

YOH (5 mg/kg),

significantly

in saline-trea in SV-treated

reduced GAS in saline-

enhanced the inhibitory

effect

PRZ (1 mg/kg) and PRP (4 mg/kg) failed

modify the response to the peptide, 1043-6618/90/2210013-02/$03.00/0

in acid output

rats

while HLP (0.5 mg/kg) significantly

of to po-

o 1990TheItalianPharmacological Society

14

Pharmacological

tentiated dify

antisecretory

effect

basal GAS (216.0ju~q),

its

while

induced by SV (12.6

(TABLE I).

Research,

Indomethacin

enhancing the inhibition

Vol. 22, Supplement

I,1990

alone did not moof acid output

PEq).

TABLE I Effects of peripherally (ip) administered catecholamine antagonists on SVinduced inhibition of gastric acid secretion in pylorus-ligated rats. Treatment

Noof rats

Saline sv

PHE PHE+ SV YOH YOH + SV PRZ PRz-t sv PRP PRP -k SV HLP i&P+-sv

Volume bvN

11 11 10 10 10 10 10 10 10 10 10 10

3.1 1.0 1.4 0.5 2.0 1.2 2.7 1.1 2.7 1.2 3.5 0.4

2 0.51 + 0.24 -f: 0.28 f 0.07 5 0.12 t 0.24 i 0.18 + 0.25 10.66 + 0.13 + 0.42 + 0.02

Acid output ( pEq/a)

PH 2.04 3.71 2.82 5.22 1.60 3.60 1.90 3.80 2.50 5.00 1.84 6.23

9 '4 -:a "§ -::"5 +t "I -::"§ -::-0

+ 0.18 + 0.49 + 0.39 k 0.67 + 0.23 10.45 10.31 f 0.54 + 0.32 f 0.65 10.08 2 0.35

Each value is the mean -f: S.E.M.; %= P< 0.01 $ = PCO.01 vs antagonist I- SV j o = PC 0.01

* I 3~ "I 3s "5 + "5 -::"$ +:-o

302.3 52.7 150.3 24.6 253.4 52.8 220.2 50.0 264.4 56.3 406.0 8.5

+ 59.3 2 11.4 s f 37.1 +:-o$ + 7.80 ~0 127.3 "§ + 9.5 3:f 38.2 "I f 13.5 -:: i: 63.9 "I + 20.1 3:f 51.0 -:q f 2.50 +cO

vs each own control; vs SV group.

CONCLUSIONS This study confirms GAS in conscious diating

However, further

glands play a role

Moreover,

between the peptide

and prostaglsndin treatment

of SV significantly

The adrenal

response to the peptide.

creased potency after of SV antiacid

injections

rats.

of some interference

dopaminergic

thacin.

subcutaneous

pylorus-ligated

the gastric

the existence gic,

that

systems, be-use

with phentolamine,

informations

reduced in me-

we can not exclude and the h-adrener of the peptide's

haloperidol

are needed to elucidate

in-

and indomethe mechanism

effect.

REFERENCES 1) Erspamer V, Erspamer Falconieri G, Improta G, Negri L, De Castiglione R. Sauvagine, a new polypeptide from Phyllomedusa Sauvagei skin. W-S Arch. Pharmacol. 1980; 312: 265-70 2) Brown MR, Fisher LA, Spiess J, Rivier J, Rivier C, Vale W. Comparison of the biologic actions of corticotropin-releasing factor and sauvagine. Reg. Peptides 1982; 4: 107-14. 3) Improta G, Broccardo M. Sauvagine: effects cn gastric acid secretion in Peptides 1988; 9: 843-46. rats.