Abstract
We evaluated an acinar cell line (SMG-C10) cloned from rat submandibular glands as a possible model for α1-adrenoceptor regulation of submandibular function. α1-Adrenoceptors are subdivided into three subtypes called α1A, α1B, and α1D, which can be distinguished from one another by their differential affinity values for subtype-selective α1- adrenoceptor antagonists. Thus, α1-adrenoceptor subtypes in SMG-C10 cells were characterized with reverse transcription-polymerase chain reaction (RT-PCR) and [3H]prazosin binding in side-by-side experiments with native submandibular glands. RT-PCR identified mRNAs for α1A-, α1B-, and α1D- adrenoceptors in SMG-C10 cells and submandibular glands. The inhibition of [3H]prazosin binding by 5-methylurapidil (α1A- selective) was biphasic and fit best to a two-site binding model with 40 ± 8% high (KiH)- and 60 ± 10% low (K iL)-affinity binding sites in SMG-C10 cells, and 76% high- and 24% low-affinity binding sites in submandibular glands. Respective KiH and KiL values for 5-methylurapidil were 1.9 ± 0.4 and 100 ± 30 nM in SMG-C10 cells and 3.2 ± 0.8 and 170 ± 20 nM in submandibular glands. BMY-7378 [8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- 8-azaspiro[4.5]decane-7,9-dione dihydrochloride (α1D-selective) ] bound with low affinity in SMG-C10 cells and submandibular glands with K i values of 81 ± 20 and 110 ± 20 nM, respectively. Chloroethylclondine, an irreversible alkylating agent selective for α1B adrenoceptors, reduced the density of [3H] prazosin binding sites by 42 and 26% in SMG-C10 and submandibular membranes, respectively. Thus, SMG-C10 cells and submandibular glands are similar in expressing receptor protein for α1A- and α1B- adrenoceptor subtypes, establishing SMG-C10 cells as a potential model for α1-adrenoceptor-mediated secretion.
| Original language | English |
|---|---|
| Pages (from-to) | 364-372 |
| Number of pages | 9 |
| Journal | Journal of Pharmacology and Experimental Therapeutics |
| Volume | 311 |
| Issue number | 1 |
| DOIs | |
| State | Published - Oct 2004 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
Cite this
Submandibular gland acinar cells express multiple α1- adrenoceptor subtypes. / Bockman, Charles; Bruchas, Michael R.; Zeng, Wanyun; O'Connell, Kelly A.; Abel, Peter W.; Scofield, Margaret A.; Dowd, Frank J.
In: Journal of Pharmacology and Experimental Therapeutics, Vol. 311, No. 1, 10.2004, p. 364-372.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Submandibular gland acinar cells express multiple α1- adrenoceptor subtypes
AU - Bockman, Charles
AU - Bruchas, Michael R.
AU - Zeng, Wanyun
AU - O'Connell, Kelly A.
AU - Abel, Peter W.
AU - Scofield, Margaret A.
AU - Dowd, Frank J.
PY - 2004/10
Y1 - 2004/10
N2 - We evaluated an acinar cell line (SMG-C10) cloned from rat submandibular glands as a possible model for α1-adrenoceptor regulation of submandibular function. α1-Adrenoceptors are subdivided into three subtypes called α1A, α1B, and α1D, which can be distinguished from one another by their differential affinity values for subtype-selective α1- adrenoceptor antagonists. Thus, α1-adrenoceptor subtypes in SMG-C10 cells were characterized with reverse transcription-polymerase chain reaction (RT-PCR) and [3H]prazosin binding in side-by-side experiments with native submandibular glands. RT-PCR identified mRNAs for α1A-, α1B-, and α1D- adrenoceptors in SMG-C10 cells and submandibular glands. The inhibition of [3H]prazosin binding by 5-methylurapidil (α1A- selective) was biphasic and fit best to a two-site binding model with 40 ± 8% high (KiH)- and 60 ± 10% low (K iL)-affinity binding sites in SMG-C10 cells, and 76% high- and 24% low-affinity binding sites in submandibular glands. Respective KiH and KiL values for 5-methylurapidil were 1.9 ± 0.4 and 100 ± 30 nM in SMG-C10 cells and 3.2 ± 0.8 and 170 ± 20 nM in submandibular glands. BMY-7378 [8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- 8-azaspiro[4.5]decane-7,9-dione dihydrochloride (α1D-selective) ] bound with low affinity in SMG-C10 cells and submandibular glands with K i values of 81 ± 20 and 110 ± 20 nM, respectively. Chloroethylclondine, an irreversible alkylating agent selective for α1B adrenoceptors, reduced the density of [3H] prazosin binding sites by 42 and 26% in SMG-C10 and submandibular membranes, respectively. Thus, SMG-C10 cells and submandibular glands are similar in expressing receptor protein for α1A- and α1B- adrenoceptor subtypes, establishing SMG-C10 cells as a potential model for α1-adrenoceptor-mediated secretion.
AB - We evaluated an acinar cell line (SMG-C10) cloned from rat submandibular glands as a possible model for α1-adrenoceptor regulation of submandibular function. α1-Adrenoceptors are subdivided into three subtypes called α1A, α1B, and α1D, which can be distinguished from one another by their differential affinity values for subtype-selective α1- adrenoceptor antagonists. Thus, α1-adrenoceptor subtypes in SMG-C10 cells were characterized with reverse transcription-polymerase chain reaction (RT-PCR) and [3H]prazosin binding in side-by-side experiments with native submandibular glands. RT-PCR identified mRNAs for α1A-, α1B-, and α1D- adrenoceptors in SMG-C10 cells and submandibular glands. The inhibition of [3H]prazosin binding by 5-methylurapidil (α1A- selective) was biphasic and fit best to a two-site binding model with 40 ± 8% high (KiH)- and 60 ± 10% low (K iL)-affinity binding sites in SMG-C10 cells, and 76% high- and 24% low-affinity binding sites in submandibular glands. Respective KiH and KiL values for 5-methylurapidil were 1.9 ± 0.4 and 100 ± 30 nM in SMG-C10 cells and 3.2 ± 0.8 and 170 ± 20 nM in submandibular glands. BMY-7378 [8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- 8-azaspiro[4.5]decane-7,9-dione dihydrochloride (α1D-selective) ] bound with low affinity in SMG-C10 cells and submandibular glands with K i values of 81 ± 20 and 110 ± 20 nM, respectively. Chloroethylclondine, an irreversible alkylating agent selective for α1B adrenoceptors, reduced the density of [3H] prazosin binding sites by 42 and 26% in SMG-C10 and submandibular membranes, respectively. Thus, SMG-C10 cells and submandibular glands are similar in expressing receptor protein for α1A- and α1B- adrenoceptor subtypes, establishing SMG-C10 cells as a potential model for α1-adrenoceptor-mediated secretion.
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U2 - 10.1124/jpet.104.066399
DO - 10.1124/jpet.104.066399
M3 - Article
VL - 311
SP - 364
EP - 372
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
SN - 0022-3565
IS - 1
ER -