Species differences in alpha 2-adrenergic regulation of platelet adenylate cyclase.

T. A. Slotkin, E. C. McCook, Charles Nemeroff, F. J. Seidler

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Species differences in the ability of alpha 2-adrenergic receptors to down-regulate platelet adenylate cyclase activity were compared in platelet membranes derived from man, rabbit and rat. In all three, prostaglandin E1 and forskolin caused massive stimulation of enzyme activity, without species selectivity. However, alpha 2-receptor actions revealed marked species dissimilarities: clonidine caused 20-30% inhibition of human and rabbit basal adenylate cyclase, prostaglandin E1-stimulated activity and forskolin-stimulated activity, but failed to inhibit activity in the rat preparation. [3H]Rauwolscine binding indicated that rat platelets are deficient in alpha 2-receptor sites. Because rat brain is not deficient in alpha 2-receptors, these results indicate that care should be exercised in the use of platelet systems in animal models of psychotropic drug administration. Furthermore, although clonidine was effective in both man and rabbit, differences in sensitivity to alpha 2-receptor stimulation were also apparent; clonidine was more effective in inhibiting the response to prostaglandin E1 in man, but inhibition of the forskolin response was more prominent in the rabbit. Accordingly, multiple modes of stimulation need to be examined in delineating the inhibitory control of adenylate cyclase by alpha 2-receptors.

Original languageEnglish
Pages (from-to)259-271
Number of pages13
JournalResearch Communications in Chemical Pathology and Pharmacology
Volume72
Issue number3
StatePublished - Jun 1 1991
Externally publishedYes

Fingerprint

Platelets
Adenylyl Cyclases
Adrenergic Agents
Rats
Alprostadil
Clonidine
Colforsin
Blood Platelets
Rabbits
Adrenergic alpha-2 Receptors
Yohimbine
Psychotropic Drugs
Enzyme activity
Brain
Animals
Down-Regulation
Animal Models
Membranes
Enzymes

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Species differences in alpha 2-adrenergic regulation of platelet adenylate cyclase. / Slotkin, T. A.; McCook, E. C.; Nemeroff, Charles; Seidler, F. J.

In: Research Communications in Chemical Pathology and Pharmacology, Vol. 72, No. 3, 01.06.1991, p. 259-271.

Research output: Contribution to journalArticle

@article{dab12b20cc9a4b54be0b692798392197,
title = "Species differences in alpha 2-adrenergic regulation of platelet adenylate cyclase.",
abstract = "Species differences in the ability of alpha 2-adrenergic receptors to down-regulate platelet adenylate cyclase activity were compared in platelet membranes derived from man, rabbit and rat. In all three, prostaglandin E1 and forskolin caused massive stimulation of enzyme activity, without species selectivity. However, alpha 2-receptor actions revealed marked species dissimilarities: clonidine caused 20-30{\%} inhibition of human and rabbit basal adenylate cyclase, prostaglandin E1-stimulated activity and forskolin-stimulated activity, but failed to inhibit activity in the rat preparation. [3H]Rauwolscine binding indicated that rat platelets are deficient in alpha 2-receptor sites. Because rat brain is not deficient in alpha 2-receptors, these results indicate that care should be exercised in the use of platelet systems in animal models of psychotropic drug administration. Furthermore, although clonidine was effective in both man and rabbit, differences in sensitivity to alpha 2-receptor stimulation were also apparent; clonidine was more effective in inhibiting the response to prostaglandin E1 in man, but inhibition of the forskolin response was more prominent in the rabbit. Accordingly, multiple modes of stimulation need to be examined in delineating the inhibitory control of adenylate cyclase by alpha 2-receptors.",
author = "Slotkin, {T. A.} and McCook, {E. C.} and Charles Nemeroff and Seidler, {F. J.}",
year = "1991",
month = "6",
day = "1",
language = "English",
volume = "72",
pages = "259--271",
journal = "Research Communications in Molecular Pathology and Pharmacology",
issn = "0034-5164",
publisher = "PJD Publications Ltd",
number = "3",

}

TY - JOUR

T1 - Species differences in alpha 2-adrenergic regulation of platelet adenylate cyclase.

AU - Slotkin, T. A.

AU - McCook, E. C.

AU - Nemeroff, Charles

AU - Seidler, F. J.

PY - 1991/6/1

Y1 - 1991/6/1

N2 - Species differences in the ability of alpha 2-adrenergic receptors to down-regulate platelet adenylate cyclase activity were compared in platelet membranes derived from man, rabbit and rat. In all three, prostaglandin E1 and forskolin caused massive stimulation of enzyme activity, without species selectivity. However, alpha 2-receptor actions revealed marked species dissimilarities: clonidine caused 20-30% inhibition of human and rabbit basal adenylate cyclase, prostaglandin E1-stimulated activity and forskolin-stimulated activity, but failed to inhibit activity in the rat preparation. [3H]Rauwolscine binding indicated that rat platelets are deficient in alpha 2-receptor sites. Because rat brain is not deficient in alpha 2-receptors, these results indicate that care should be exercised in the use of platelet systems in animal models of psychotropic drug administration. Furthermore, although clonidine was effective in both man and rabbit, differences in sensitivity to alpha 2-receptor stimulation were also apparent; clonidine was more effective in inhibiting the response to prostaglandin E1 in man, but inhibition of the forskolin response was more prominent in the rabbit. Accordingly, multiple modes of stimulation need to be examined in delineating the inhibitory control of adenylate cyclase by alpha 2-receptors.

AB - Species differences in the ability of alpha 2-adrenergic receptors to down-regulate platelet adenylate cyclase activity were compared in platelet membranes derived from man, rabbit and rat. In all three, prostaglandin E1 and forskolin caused massive stimulation of enzyme activity, without species selectivity. However, alpha 2-receptor actions revealed marked species dissimilarities: clonidine caused 20-30% inhibition of human and rabbit basal adenylate cyclase, prostaglandin E1-stimulated activity and forskolin-stimulated activity, but failed to inhibit activity in the rat preparation. [3H]Rauwolscine binding indicated that rat platelets are deficient in alpha 2-receptor sites. Because rat brain is not deficient in alpha 2-receptors, these results indicate that care should be exercised in the use of platelet systems in animal models of psychotropic drug administration. Furthermore, although clonidine was effective in both man and rabbit, differences in sensitivity to alpha 2-receptor stimulation were also apparent; clonidine was more effective in inhibiting the response to prostaglandin E1 in man, but inhibition of the forskolin response was more prominent in the rabbit. Accordingly, multiple modes of stimulation need to be examined in delineating the inhibitory control of adenylate cyclase by alpha 2-receptors.

UR - http://www.scopus.com/inward/record.url?scp=0026176380&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026176380&partnerID=8YFLogxK

M3 - Article

C2 - 1658886

AN - SCOPUS:0026176380

VL - 72

SP - 259

EP - 271

JO - Research Communications in Molecular Pathology and Pharmacology

JF - Research Communications in Molecular Pathology and Pharmacology

SN - 0034-5164

IS - 3

ER -