Korean J Physiol Pharmacol.  2009 Dec;13(6):517-526. 10.4196/kjpp.2009.13.6.517.

Polyphenols of Rubus coreanum Inhibit Catecholamine Secretion from the Perfused Adrenal Medulla of SHRs

• Yu BS
• Na DM
• Kang MY
• Lim DY

• KMID: 2285390
• DOI: http://doi.org/10.4196/kjpp.2009.13.6.517

Abstract

The present study was attempted to investigate whether polyphenolic compounds isolated from wine, which is brewed from Rubus coreanum Miquel (PCRC), may affect the release of catecholamines (CA) from the isolated perfused adrenal medulla of the spontaneously hypertensive rats (SHRs), and to establish its mechanism of action. PCRC (20~180 microgram/ml) perfused into an adrenal vein for 90 min relatively dose-dependently inhibited the CA secretory responses to ACh (5.32 mM), high K+ (56 mM), DMPP (100 micrometer) and McN-A-343 (100 micrometer). PCRC itself did not affect basal CA secretion (data not shown). Also, in the presence of PCRC (60 microgram/ml), the CA secretory responses to veratridine (a selective Na+ channel activator (10 micrometer), Bay-K-8644 (a L-type dihydropyridine Ca2+ channel activator, 10 micrometer), and cyclopiazonic acid (a cytoplasmic Ca2+ -ATPase inhibitor, 10 micrometer) were significantly reduced, respectively. In the simultaneous presence of PCRC (60 microgram/ml) and L-NAME (an inhibitor of NO synthase, 30 micrometer), the inhibitory responses of PCRC on the CA secretion evoked by ACh, high K+, DMPP, and Bay-K-8644 were considerably recovered to the extent of the corresponding control secretion compared with that of PCRC-treatment alone. The level of NO released from adrenal medulla after the treatment of PCRC (60 microgram/ml) was greatly elevated compared with the corresponding basal level. Taken together, these results demonstrate that PCRC inhibits the CA secretion from the isolated perfused adrenal medulla of the SHRs evoked by stimulation of cholinergic receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of PCRC is mediated by blocking the influx of calcium and sodium into the adrenal medullary chromaffin cells of the SHRs as well as by inhibition of Ca2+ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of NO synthase.

Keyword

PCRC; Catecholamine secretion; Adrenal medulla; Cholinergic receptors; Nitric oxide

MeSH Terms

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Adrenal Medulla
Calcium
Catecholamines
Chromaffin Cells
Cytoplasm
Dihydropyridines
Dimethylphenylpiperazinium Iodide
Indoles
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Polyphenols
Rats, Inbred SHR
Receptors, Cholinergic
Sodium
Veins
Veratridine
Wine
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Calcium
Catecholamines
Dihydropyridines
Dimethylphenylpiperazinium Iodide
Indoles
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Polyphenols
Receptors, Cholinergic
Sodium
Veratridine

Figure

• 

  Fig. 1. Preparation of polyphenolic compounds from Rubus coreanum Miquel (PCRC). Yield of polyphenolic compounds from Bokboonja wine expressed with grams per liter.

• 

  Fig. 2. Dose-dependent effects of PCRC on the secretory responses of catecholamines (CA) evoked by acetylcholine (upper) and high potassium (lower) from the perfused rat adrenal medulla. The CA secretion by a single injection of ACh (5.32 mM) and K+ (56 mM) in a volume of 0.05 ml was evoked at 15 min intervals during loading with 20, 60 and 180 μg/ml of PCRC for 90 min as indicated by the arrow marks, respectively. The numbers in parentheses indicate the number of rat adrenal glands. Vertical bars on the columns represent the standard error of the mean (S.E.M.). Ordinate: the amounts of CA secreted from the adrenal gland (% of control). Abscissa: collection time of perfusate (min). Statistical difference was obtained by comparing the corresponding control (CONTROL) with each concentration-treated group of PCRC. ACh-and high K+-induced perfusates were collected for 4 minutes, respectively. ∗∗p<0.01. ns: Not statistically significant.

• 

  Fig. 3. Dose-dependent effects of PCRC on the CA secretory responses evoked by DMPP (upper) and McN-A-343 (lower) from the perfused rat adrenal medulla. The CA secretion by perfusion of DMPP (100 μM) for 1 min and McN-A-343 (100 μM) for 4 min was induced at 20 and 15 min intervals during loading with 20, 60 and 180 μg/ml of PCRC for 90 min, respectively. Statistical difference was obtained by comparing the corresponding control (CONTROL) with each concentration-pretreated group of PCRC. DMPP- and McN- A-343-induced perfusates were collected for 8 and 4 minutes, respectively. Other legends are the same as in Fig. 2. ∗p<0.05, ∗∗p<0.01. ns: Not statistically significant.

• 

  Fig. 4. Time-course effects of PCRC on the CA secretion evoked by Bay-K-8644 (upper) and cyclopiazonic acid (lower) from the perfused rat adrenal medulla. Bay-K-8644 (10 μM) and cyclopiazonic acid (10 μM) were perfused into an adrenal vein for 4 min at 15 min intervals during loading with PCRC (60 μg/ml) for 90 min. Other legends are the same as in Fig. 2. ∗p<0.05, ∗∗p<0.01. ns: Not statistically significant.

• 

  Fig. 5. Time-course effects of PCRC on the CA secretion evoked by veratridine from the perfused rat adrenal medulla. Veratridine (100 μM) was perfused into an adrenal vein for 4 min at 15 min intervals during loading with PCRC (60 μg/ml) for 90 min. Other legends are the same as in Fig. 2. ∗∗p<0.01.

• 

  Fig. 6. Influence of PCRC plus L-NAME on the CA secretory responses evoked by acetylcholine (upper) and high potassium (lower) from the perfused rat adrenal medulla. The CA secretion by a single injection of ACh (5.32 mM) and K+ (56 mM) in a volume of 0.05 ml was evoked at 15 min intervals during simultaneous loading with PCRC (60 μg/ml) plus L-NAME (30 μM) for 90 min. Statistical difference was obtained by comparing the corresponding control (CONTROL) with PCRC-treated group or group treated with PCRC + L-NAME. Other legends are the same as in Fig. 2. ∗∗p<0.01. ns: Not statistically significant.

• 

  Fig. 7. Influence of PCRC plus L-NAME on the CA secretory responses evoked by DMPP (upper) and McN-A-343 (lower) from the perfused rat adrenal medulla. The CA secretion by perfusion of DMPP (100 μM) for 1 min and McN-A-343 (100 μM) for 4 min was induced at 20 and 15 min intervals after preloading with PCRC (60 μg/ml) plus L-NAME (30 μM) for 90 min, respectively. Other legends are the same as in Fig. 2 and 6. ∗∗p<0.01. ns: Not statistically significant.

• 

  Fig. 8. Influence of PCRC plus L-NAME on the CA secretory responses evoked by Bay-K-8644 (upper) and cyclopiazonic acid (lower) from the perfused rat adrenal medulla. Bay-K-8644 (10 μM) and cyclopiazonic acid (10 μM) were perfused into an adrenal vein for 4 min at 15 min intervals during simultaneous loading with PCRC (60 μg/ml) for 90 min. Other legends are the same as in Fig. 2 and 6. ∗p<0.05, ∗∗p<0.01. ns: Not statistically significant.

• 

  Fig. 9. Influence of of PCRC on nitric oxide (NO) production in the perfused rat adrenal medulla. Perfusate sample was taken for 8 min after loading the perfusion of PCRC (180 μg/ml) at a rate of 0.31 ml/min. Ordinate: the amounts of NO released from the adrenal medulla (% of control). Abscissa: Treatment (before and after PCRC). Statistical difference was made by comparing the control with PCRC-treated group. ∗∗p<0.01.

Reference

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