6-Keto-PGE1 exhibits more potent bronchodilatory activity in the cat than its precursor, PGI2

Ernst Wm Spannhake; James L. Levin; Albert L. Hyman; Philip J. Kadowitz

doi:10.1016/0090-6980(81)90144-1

6-Keto-PGE₁ exhibits more potent bronchodilatory activity in the cat than its precursor, PGI₂

Ernst Wm Spannhake, James L. Levin, Albert L. Hyman, Philip J. Kadowitz

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Abstract

In anesthetized, vagotomized and mechanically ventilated cats, we investigated the bronchodilatory activity of the PGI₂ metabolite, 6-keto-PGE₁, relative to PGI₂ and PGE₂. In a range of doses from 0.3-10.0 μg, i.v. injection of 6-keto-PGE₁ produced a dose-related decrease in central airway resistance (R_L) in animals bronchoconstricted by 5-HT. This effect on R_L was 3-10 times greater than that produced by i.v. PGI₂. At the lower doses, 6-keto-PGE₁ was also more potent than PGI₂ in increasing dynamic lung compliance; their effects upon semi-static compliance were not significantly different. Comparison of the bronchopulmonary effects of the two prostanoids did not show any consistent difference in their temporal patterns. In contrast to PGI₂ or PGE₂, 6-keto-PGE₁ had minimal pulmonary vasomotor activity. Inhibition of the cyclooxygenase pathway with sodium meclofenamate had no effect on the bronchopulmonary actions of 6-keto-PGE₁ or on its duration of action. These data indicate that 6-keto-PGE₁ is a more potent bronchodilator than PGI₂ in the cat. They further suggest that conversion of PGI₂ to 6-keto-PGE₁, if it occurs to an appreciable extent in the lung in vivo, could enhance bronchodilatory activity.

Original language	English (US)
Pages (from-to)	267-275
Number of pages	9
Journal	Prostaglandins
Volume	21
Issue number	2
DOIs	https://doi.org/10.1016/0090-6980(81)90144-1
State	Published - Feb 1981
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Endocrinology

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10.1016/0090-6980(81)90144-1

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@article{71827f1c86bd409ea7e4eb1b23cfc52f,

title = "6-Keto-PGE1 exhibits more potent bronchodilatory activity in the cat than its precursor, PGI2",

abstract = "In anesthetized, vagotomized and mechanically ventilated cats, we investigated the bronchodilatory activity of the PGI2 metabolite, 6-keto-PGE1, relative to PGI2 and PGE2. In a range of doses from 0.3-10.0 μg, i.v. injection of 6-keto-PGE1 produced a dose-related decrease in central airway resistance (RL) in animals bronchoconstricted by 5-HT. This effect on RL was 3-10 times greater than that produced by i.v. PGI2. At the lower doses, 6-keto-PGE1 was also more potent than PGI2 in increasing dynamic lung compliance; their effects upon semi-static compliance were not significantly different. Comparison of the bronchopulmonary effects of the two prostanoids did not show any consistent difference in their temporal patterns. In contrast to PGI2 or PGE2, 6-keto-PGE1 had minimal pulmonary vasomotor activity. Inhibition of the cyclooxygenase pathway with sodium meclofenamate had no effect on the bronchopulmonary actions of 6-keto-PGE1 or on its duration of action. These data indicate that 6-keto-PGE1 is a more potent bronchodilator than PGI2 in the cat. They further suggest that conversion of PGI2 to 6-keto-PGE1, if it occurs to an appreciable extent in the lung in vivo, could enhance bronchodilatory activity.",

author = "Spannhake, {Ernst Wm} and Levin, {James L.} and Hyman, {Albert L.} and Kadowitz, {Philip J.}",

note = "Funding Information: The authors would like to thank Ms. Alice Landry for excellent technical assistance and Ms. Janice Ignarro for expert preparation ofthemanuscript. This work was supported by grants HL 22945, HL 11802 and HL 18070 from the National Institutes of Health.",

year = "1981",

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doi = "10.1016/0090-6980(81)90144-1",

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T1 - 6-Keto-PGE1 exhibits more potent bronchodilatory activity in the cat than its precursor, PGI2

AU - Spannhake, Ernst Wm

AU - Levin, James L.

AU - Hyman, Albert L.

AU - Kadowitz, Philip J.

N1 - Funding Information: The authors would like to thank Ms. Alice Landry for excellent technical assistance and Ms. Janice Ignarro for expert preparation ofthemanuscript. This work was supported by grants HL 22945, HL 11802 and HL 18070 from the National Institutes of Health.

PY - 1981/2

Y1 - 1981/2

N2 - In anesthetized, vagotomized and mechanically ventilated cats, we investigated the bronchodilatory activity of the PGI2 metabolite, 6-keto-PGE1, relative to PGI2 and PGE2. In a range of doses from 0.3-10.0 μg, i.v. injection of 6-keto-PGE1 produced a dose-related decrease in central airway resistance (RL) in animals bronchoconstricted by 5-HT. This effect on RL was 3-10 times greater than that produced by i.v. PGI2. At the lower doses, 6-keto-PGE1 was also more potent than PGI2 in increasing dynamic lung compliance; their effects upon semi-static compliance were not significantly different. Comparison of the bronchopulmonary effects of the two prostanoids did not show any consistent difference in their temporal patterns. In contrast to PGI2 or PGE2, 6-keto-PGE1 had minimal pulmonary vasomotor activity. Inhibition of the cyclooxygenase pathway with sodium meclofenamate had no effect on the bronchopulmonary actions of 6-keto-PGE1 or on its duration of action. These data indicate that 6-keto-PGE1 is a more potent bronchodilator than PGI2 in the cat. They further suggest that conversion of PGI2 to 6-keto-PGE1, if it occurs to an appreciable extent in the lung in vivo, could enhance bronchodilatory activity.

AB - In anesthetized, vagotomized and mechanically ventilated cats, we investigated the bronchodilatory activity of the PGI2 metabolite, 6-keto-PGE1, relative to PGI2 and PGE2. In a range of doses from 0.3-10.0 μg, i.v. injection of 6-keto-PGE1 produced a dose-related decrease in central airway resistance (RL) in animals bronchoconstricted by 5-HT. This effect on RL was 3-10 times greater than that produced by i.v. PGI2. At the lower doses, 6-keto-PGE1 was also more potent than PGI2 in increasing dynamic lung compliance; their effects upon semi-static compliance were not significantly different. Comparison of the bronchopulmonary effects of the two prostanoids did not show any consistent difference in their temporal patterns. In contrast to PGI2 or PGE2, 6-keto-PGE1 had minimal pulmonary vasomotor activity. Inhibition of the cyclooxygenase pathway with sodium meclofenamate had no effect on the bronchopulmonary actions of 6-keto-PGE1 or on its duration of action. These data indicate that 6-keto-PGE1 is a more potent bronchodilator than PGI2 in the cat. They further suggest that conversion of PGI2 to 6-keto-PGE1, if it occurs to an appreciable extent in the lung in vivo, could enhance bronchodilatory activity.

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6-Keto-PGE₁ exhibits more potent bronchodilatory activity in the cat than its precursor, PGI₂

Abstract

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