Abstract
Purpose: To determine the serotonergic (5HT) receptor subtype mediating the contraction of bovine posterior ciliary arteries (BPCAs) in vitro. Methods: Longitudinal isometric tension was measured in BPCA strips (4-5 mm) mounted in 25 mL organ baths containing oxygenated Krebs solution at 37°C. Cumulative contractile concentration-response (C-R) curves were generated for various 5-HT agonists to assess their potencies and maximal degrees of contraction. Multiple agonist C-R curves were also constructed in the presence and absence of receptor-selective antagonists to determine antagonist potencies using Schild plots. Results: Selective and nonselective agonists for 5-HT receptors elicited concentration-dependent contractile responses in BPCAs with the following rank order of potency: MK-212 > BW723C86 > α-methyl-5-HT >5-methoxy-α-5-methyl-5-HT >> R-DO1 > >5-HT >> cabergoline >> 5-methoxy-dimethyl-tryptamine >> 2-methyl-5-HT >> tryptamine. Interestingly, both 8-OH-DPAT (5HT1A agonist) and quipazine (5HT3 agonist) did not elicit contractions in BPCAs. The contractions produced by BW723C86 (5-HT2B agonist) were antagonized by 5-HT receptor blockers, RS-127445 (5-HT2B antagonist), and M-100907 (5-HT2A antagonist), yielding antagonist pA2 values of 7.5 ± 0.12 (n = 4) and 6.2 ± 0.17 (n = 4), respectively. Furthermore, contractions elicited by MK-212 (5-HT2C agonist) was blocked by RS-102221 (5-HT2C antagonist), although noncompetitively. Conclusions: On the basis of the pharmacological profile of selective agonists and antagonists, we conclude that serotonin-induced contractions of the BPCA are mediated primarily by a combination of 5HT2C and/or 5HT2B receptors. It appears that 5-HT1A and 5-HT3 receptors are not involved in the contractile action of BPCAs to serotonin.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 134-140 |
| Number of pages | 7 |
| Journal | Journal of Ocular Pharmacology and Therapeutics |
| Volume | 34 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Jan 1 2018 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Ophthalmology
- Pharmacology
- Pharmacology (medical)
Cite this
Pharmacology of serotonin receptors causing contraction of isolated bovine posterior ciliary arteries : Role in ocular blood flow. / Njie-Mbye, Ya Fatou; Robinson, Jenaye; Mitchell-Bush, Leah; McKoy, Marshalyn; Opere, Catherine A.; Ohia, Sunny E.; Sharif, Naj.
In: Journal of Ocular Pharmacology and Therapeutics, Vol. 34, No. 1-2, 01.01.2018, p. 134-140.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pharmacology of serotonin receptors causing contraction of isolated bovine posterior ciliary arteries
T2 - Role in ocular blood flow
AU - Njie-Mbye, Ya Fatou
AU - Robinson, Jenaye
AU - Mitchell-Bush, Leah
AU - McKoy, Marshalyn
AU - Opere, Catherine A.
AU - Ohia, Sunny E.
AU - Sharif, Naj
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Purpose: To determine the serotonergic (5HT) receptor subtype mediating the contraction of bovine posterior ciliary arteries (BPCAs) in vitro. Methods: Longitudinal isometric tension was measured in BPCA strips (4-5 mm) mounted in 25 mL organ baths containing oxygenated Krebs solution at 37°C. Cumulative contractile concentration-response (C-R) curves were generated for various 5-HT agonists to assess their potencies and maximal degrees of contraction. Multiple agonist C-R curves were also constructed in the presence and absence of receptor-selective antagonists to determine antagonist potencies using Schild plots. Results: Selective and nonselective agonists for 5-HT receptors elicited concentration-dependent contractile responses in BPCAs with the following rank order of potency: MK-212 > BW723C86 > α-methyl-5-HT >5-methoxy-α-5-methyl-5-HT >> R-DO1 > >5-HT >> cabergoline >> 5-methoxy-dimethyl-tryptamine >> 2-methyl-5-HT >> tryptamine. Interestingly, both 8-OH-DPAT (5HT1A agonist) and quipazine (5HT3 agonist) did not elicit contractions in BPCAs. The contractions produced by BW723C86 (5-HT2B agonist) were antagonized by 5-HT receptor blockers, RS-127445 (5-HT2B antagonist), and M-100907 (5-HT2A antagonist), yielding antagonist pA2 values of 7.5 ± 0.12 (n = 4) and 6.2 ± 0.17 (n = 4), respectively. Furthermore, contractions elicited by MK-212 (5-HT2C agonist) was blocked by RS-102221 (5-HT2C antagonist), although noncompetitively. Conclusions: On the basis of the pharmacological profile of selective agonists and antagonists, we conclude that serotonin-induced contractions of the BPCA are mediated primarily by a combination of 5HT2C and/or 5HT2B receptors. It appears that 5-HT1A and 5-HT3 receptors are not involved in the contractile action of BPCAs to serotonin.
AB - Purpose: To determine the serotonergic (5HT) receptor subtype mediating the contraction of bovine posterior ciliary arteries (BPCAs) in vitro. Methods: Longitudinal isometric tension was measured in BPCA strips (4-5 mm) mounted in 25 mL organ baths containing oxygenated Krebs solution at 37°C. Cumulative contractile concentration-response (C-R) curves were generated for various 5-HT agonists to assess their potencies and maximal degrees of contraction. Multiple agonist C-R curves were also constructed in the presence and absence of receptor-selective antagonists to determine antagonist potencies using Schild plots. Results: Selective and nonselective agonists for 5-HT receptors elicited concentration-dependent contractile responses in BPCAs with the following rank order of potency: MK-212 > BW723C86 > α-methyl-5-HT >5-methoxy-α-5-methyl-5-HT >> R-DO1 > >5-HT >> cabergoline >> 5-methoxy-dimethyl-tryptamine >> 2-methyl-5-HT >> tryptamine. Interestingly, both 8-OH-DPAT (5HT1A agonist) and quipazine (5HT3 agonist) did not elicit contractions in BPCAs. The contractions produced by BW723C86 (5-HT2B agonist) were antagonized by 5-HT receptor blockers, RS-127445 (5-HT2B antagonist), and M-100907 (5-HT2A antagonist), yielding antagonist pA2 values of 7.5 ± 0.12 (n = 4) and 6.2 ± 0.17 (n = 4), respectively. Furthermore, contractions elicited by MK-212 (5-HT2C agonist) was blocked by RS-102221 (5-HT2C antagonist), although noncompetitively. Conclusions: On the basis of the pharmacological profile of selective agonists and antagonists, we conclude that serotonin-induced contractions of the BPCA are mediated primarily by a combination of 5HT2C and/or 5HT2B receptors. It appears that 5-HT1A and 5-HT3 receptors are not involved in the contractile action of BPCAs to serotonin.
UR - http://www.scopus.com/inward/record.url?scp=85042190100&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042190100&partnerID=8YFLogxK
U2 - 10.1089/jop.2017.0124
DO - 10.1089/jop.2017.0124
M3 - Article
VL - 34
SP - 134
EP - 140
JO - Journal of Ocular Pharmacology and Therapeutics
JF - Journal of Ocular Pharmacology and Therapeutics
SN - 1080-7683
IS - 1-2
ER -