Abstract
Although insulin release is known to be inhibited by alpha-2 adrenergic agonism, the effect of alpha adrenergic agonism on islet glucagon release remains controversial. Alpha-2 adrenoceptors are subdivided into alpha-2A and alpha-2B subtypes using receptor binding methods or cloning methodology. This study was designed to confirm the involvement of the alpha-2 adrenoceptor and its subtypes in glucagon release from the isolated, perfused rat pancreas. Both the alpha-2A preferential agonist oxymetazoline and the non-subtype-selective alpha-2 agonist clonidine induced concentration-dependent stimulation of glucagon release, starting at 10-8 and 10-7 mol/l, respectively (p < 0.01). In contrast, neither of the two alpha-1 selective agonists, methoxamine and phenylephrine, at concentrations up to 10-6 mol/l affected glucagon release. Furthermore, the non-subtype-selective alpha-2 antagonist rauwolscine at concentrations of 10-6 and 10-5 mol/l and the alpha-1 and alpha-2A selective antagonist WB-4101 at 10-5 mol/l showed significant antagonism of 10-7 mol/l clonidine-induced glucagon release versus corresponding controls. Neither the alpha-1 and alpha-2B selective antagonist prazosin nor the alpha-2B preferential antagonist chlorpromazine, at concentrations up to 10-5 mol/l, antagonized the effects of clonidine. None of the eight drugs, at the concentrations tested, affected insulin release with 5.5 mmol/l glucose. These results suggest that in rats islet glucagon release induced by alpha adrenoceptor agonism is mediated through alpha-2 adrenoceptors, possibly the alpha-2A subtype.
| Original language | English |
|---|---|
| Pages (from-to) | 279-283 |
| Number of pages | 5 |
| Journal | Acta Endocrinologica |
| Volume | 127 |
| Issue number | 3 |
| Publication status | Published - 1992 |
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ASJC Scopus subject areas
- Endocrinology
Cite this
Alpha-2 adrenergic agonism stimulates islet glucagon release from perfused rat pancreas : Possible involvement of alpha-2A adrenergic receptor subtype. / Hirose, Hiroshi; Maruyama, H.; Itoh, K.; Koyama, K.; Kido, K.; Saruta, T.
In: Acta Endocrinologica, Vol. 127, No. 3, 1992, p. 279-283.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Alpha-2 adrenergic agonism stimulates islet glucagon release from perfused rat pancreas
T2 - Possible involvement of alpha-2A adrenergic receptor subtype
AU - Hirose, Hiroshi
AU - Maruyama, H.
AU - Itoh, K.
AU - Koyama, K.
AU - Kido, K.
AU - Saruta, T.
PY - 1992
Y1 - 1992
N2 - Although insulin release is known to be inhibited by alpha-2 adrenergic agonism, the effect of alpha adrenergic agonism on islet glucagon release remains controversial. Alpha-2 adrenoceptors are subdivided into alpha-2A and alpha-2B subtypes using receptor binding methods or cloning methodology. This study was designed to confirm the involvement of the alpha-2 adrenoceptor and its subtypes in glucagon release from the isolated, perfused rat pancreas. Both the alpha-2A preferential agonist oxymetazoline and the non-subtype-selective alpha-2 agonist clonidine induced concentration-dependent stimulation of glucagon release, starting at 10-8 and 10-7 mol/l, respectively (p < 0.01). In contrast, neither of the two alpha-1 selective agonists, methoxamine and phenylephrine, at concentrations up to 10-6 mol/l affected glucagon release. Furthermore, the non-subtype-selective alpha-2 antagonist rauwolscine at concentrations of 10-6 and 10-5 mol/l and the alpha-1 and alpha-2A selective antagonist WB-4101 at 10-5 mol/l showed significant antagonism of 10-7 mol/l clonidine-induced glucagon release versus corresponding controls. Neither the alpha-1 and alpha-2B selective antagonist prazosin nor the alpha-2B preferential antagonist chlorpromazine, at concentrations up to 10-5 mol/l, antagonized the effects of clonidine. None of the eight drugs, at the concentrations tested, affected insulin release with 5.5 mmol/l glucose. These results suggest that in rats islet glucagon release induced by alpha adrenoceptor agonism is mediated through alpha-2 adrenoceptors, possibly the alpha-2A subtype.
AB - Although insulin release is known to be inhibited by alpha-2 adrenergic agonism, the effect of alpha adrenergic agonism on islet glucagon release remains controversial. Alpha-2 adrenoceptors are subdivided into alpha-2A and alpha-2B subtypes using receptor binding methods or cloning methodology. This study was designed to confirm the involvement of the alpha-2 adrenoceptor and its subtypes in glucagon release from the isolated, perfused rat pancreas. Both the alpha-2A preferential agonist oxymetazoline and the non-subtype-selective alpha-2 agonist clonidine induced concentration-dependent stimulation of glucagon release, starting at 10-8 and 10-7 mol/l, respectively (p < 0.01). In contrast, neither of the two alpha-1 selective agonists, methoxamine and phenylephrine, at concentrations up to 10-6 mol/l affected glucagon release. Furthermore, the non-subtype-selective alpha-2 antagonist rauwolscine at concentrations of 10-6 and 10-5 mol/l and the alpha-1 and alpha-2A selective antagonist WB-4101 at 10-5 mol/l showed significant antagonism of 10-7 mol/l clonidine-induced glucagon release versus corresponding controls. Neither the alpha-1 and alpha-2B selective antagonist prazosin nor the alpha-2B preferential antagonist chlorpromazine, at concentrations up to 10-5 mol/l, antagonized the effects of clonidine. None of the eight drugs, at the concentrations tested, affected insulin release with 5.5 mmol/l glucose. These results suggest that in rats islet glucagon release induced by alpha adrenoceptor agonism is mediated through alpha-2 adrenoceptors, possibly the alpha-2A subtype.
UR - http://www.scopus.com/inward/record.url?scp=0026673641&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026673641&partnerID=8YFLogxK
M3 - Article
C2 - 1357904
AN - SCOPUS:0026673641
VL - 127
SP - 279
EP - 283
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
SN - 0804-4643
IS - 3
ER -