Pentadecapeptide BPC 157 interactions with adrenergic and dopaminergic systems in mucosal protection in stress.
Since superior protection against different gastrointestinal and liver lesions and antiinflammatory and analgesic activities were noted for pentadecapeptide BPC (an essential fragment of an organoprotective gastric juice protein named BPC), the beneficial mechanism of BPC 157 and its likely interactions with other systems were studied. Hence its beneficial effects would be abolished by adrenal gland medullectomy, the influence of different agents affecting alpha, beta, and dopamine receptors on BPC 157 gastroprotection in 48 h restraint stress was further investigated. Animals were pretreated (1 hr before stress) with saline (controls) or BPC 157 (dissolved in saline) (10 microg or 10 ng/kg body wt intraperitoneally or intragastrically) applied either alone to establish basal conditions or, when manipulating the adrenergic or dopaminergic system, a simultaneous administration was carried out with various agents with specific effects on adrenergic or dopaminergic receptors [given in milligrams per kilogram intraperitoneally except for atenolol, which was given subcutaneously] phentolamine (10.0), prazosin (0.5), yohimbine (5.0), clonidine (0.1) (alpha-adrenergic domain), propranolol (1.0), atenolol (20.0) (beta-adrenergic domain), domperidone (5.0), and haloperidol (5.0) (peripheral/central dopamine system). Alternatively, agents stimulating adrenergic or dopaminergic systems--adrenaline (5.0) or bromocriptine (10.0)--were applied. A strong protection, noted following intragastric or intraperitoneal administration of BPC 157, was fully abolished by coadministration of phentolamine, clonidine, and haloperidol, and consistently not affected by prazosin, yohimbine, or domperidone. Atenolol abolished only intraperitoneal BPC 157 protection, whereas propranolol affected specifically intragastric BPC 157 protection. Interestingly, the severe course of lesion development obtained in basal conditions, unlike BPC 157 gastroprotection, was not influenced by the application of these agents. In other experiments, when adrenaline and bromocriptine were given simultaneously, a strong reduction of lesion development was noted. However, when applied separately, only adrenaline, not bromocriptine, has a protective effect. Thus, a complex protective interaction with both alpha-adrenergic (eg, catecholamine release) and dopaminergic (central) systems could be suggested for both intragastric and intraperitoneal BPC 157 administration. The involvement of beta-receptor stimulation in BPC 157 gastroprotection appears to be related to the route of BPC 157 administration. The demonstration that a combined stimulation of adrenergic and dopaminergic systems by simultaneous prophylactic application of adrenaline (alpha- and beta-receptor stimulant) and bromocriptine (dopamine receptor agonist) may significantly reduce restraint stress lesions development provides insight for further research on the beneficial mechanism of BPC 157.
Sikirić
P
P
Department of Pharmacology, Medical Faculty, University of Zagreb, Republic of Croatia.
Mazul
B
B
Seiwerth
S
S
Grabarević
Z
Z
Rucman
R
R
Petek
M
M
Jagić
V
V
Turković
B
B
Rotkvić
I
I
Mise
S
S
Zoricić
I
I
Jurina
L
L
Konjevoda
P
P
Hanzevacki
M
M
Gjurasin
M
M
Separović
J
J
Ljubanović
D
D
Artuković
B
B
Bratulić
M
M
Tisljar
M
M
Miklić
P
P
Sumajstorcić
J
J
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010446:Peptide Fragments / Q000627:therapeutic use*; D011506:Proteins / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects*; D013276:Stomach Ulcer / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
D018663:Adrenergic Agents; D000897:Anti-Ulcer Agents; D015259:Dopamine Agents; D010446:Peptide Fragments; D011506:Proteins; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; C083833:BPC 157