The influence of guanyl-5′-yl imidodiphosphate and sodium on muscarinic receptor binding in the rat brain and longitudinal muscle of the rat ileum

Frederick J. Ehlert, William R. Roeske, Lois B. Rosenberger, Henry I. Yamamura

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

The effects of guanyl-5′-yl imidodiphosphate (Gpp(NH)p) and sodium on muscarinic receptor binding in the rat brain and longitudinal muscle of the rat ileum were investigated using the specific muscarinic affinity label [3H](-) quinuclidinyl benzilate ([3H](-)QNB). When measured by competitive inhibition of [3H](-)QNB binding to homogenates of the longitudinal muscle of the ileum, the IC50′s of oxotremorine and carbachol increased by a factor of 3 in the presence of 30 μM Gpp(NH)p. In contrast Gpp(NH)p only produced small increases in agonist IC50 values when binding experiments were done on various rat brain regions. The agonist inhibition curves deviated from the law of mass action and were consistant with a two binding site model. Nonlinear regression analysis showed variation in the percentage of high affinity agonist sites in the cerebellum (68%), brainstem (68%), longitudinal muscle of the ileum (44-50%) and forebrain (21-30%). In the ileum and forebrain, the predominant effect of Gpp(NH)p on agonist binding was a reduction in the affinity of the high affinity agonist binding site. In the cerebellum and brainstem Gpp(NH)p had no effect. Furthermore, Gpp(NH)p had no significant effect on antagonist binding in any tissue. The influence of sodium (200 mM NaCl) on muscarinic receptor binding was investigated in homogenates of the forebrain and longitudinal muscle of the ileum, and a preferential reduction of agonist affinity by sodium was observed.

Original languageEnglish (US)
Pages (from-to)245-252
Number of pages8
JournalLife Sciences
Volume26
Issue number3
DOIs
StatePublished - Jan 21 1980
Externally publishedYes

Fingerprint

Guanylyl Imidodiphosphate
Muscarinic Receptors
Ileum
Muscle
Rats
Brain
Sodium
Muscles
Prosencephalon
Cerebellum
Brain Stem
Binding Sites
Affinity Labels
Quinuclidinyl Benzilate
Oxotremorine
Carbachol
Regression analysis
Cholinergic Agents
imidodiphosphonic acid
Inhibitory Concentration 50

ASJC Scopus subject areas

  • Pharmacology

Cite this

The influence of guanyl-5′-yl imidodiphosphate and sodium on muscarinic receptor binding in the rat brain and longitudinal muscle of the rat ileum. / Ehlert, Frederick J.; Roeske, William R.; Rosenberger, Lois B.; Yamamura, Henry I.

In: Life Sciences, Vol. 26, No. 3, 21.01.1980, p. 245-252.

Research output: Contribution to journalArticle

@article{b77c19feb70f4d85971c158e2362a60a,
title = "The influence of guanyl-5′-yl imidodiphosphate and sodium on muscarinic receptor binding in the rat brain and longitudinal muscle of the rat ileum",
abstract = "The effects of guanyl-5′-yl imidodiphosphate (Gpp(NH)p) and sodium on muscarinic receptor binding in the rat brain and longitudinal muscle of the rat ileum were investigated using the specific muscarinic affinity label [3H](-) quinuclidinyl benzilate ([3H](-)QNB). When measured by competitive inhibition of [3H](-)QNB binding to homogenates of the longitudinal muscle of the ileum, the IC50′s of oxotremorine and carbachol increased by a factor of 3 in the presence of 30 μM Gpp(NH)p. In contrast Gpp(NH)p only produced small increases in agonist IC50 values when binding experiments were done on various rat brain regions. The agonist inhibition curves deviated from the law of mass action and were consistant with a two binding site model. Nonlinear regression analysis showed variation in the percentage of high affinity agonist sites in the cerebellum (68{\%}), brainstem (68{\%}), longitudinal muscle of the ileum (44-50{\%}) and forebrain (21-30{\%}). In the ileum and forebrain, the predominant effect of Gpp(NH)p on agonist binding was a reduction in the affinity of the high affinity agonist binding site. In the cerebellum and brainstem Gpp(NH)p had no effect. Furthermore, Gpp(NH)p had no significant effect on antagonist binding in any tissue. The influence of sodium (200 mM NaCl) on muscarinic receptor binding was investigated in homogenates of the forebrain and longitudinal muscle of the ileum, and a preferential reduction of agonist affinity by sodium was observed.",
author = "Ehlert, {Frederick J.} and Roeske, {William R.} and Rosenberger, {Lois B.} and Yamamura, {Henry I.}",
year = "1980",
month = "1",
day = "21",
doi = "10.1016/0024-3205(80)90300-8",
language = "English (US)",
volume = "26",
pages = "245--252",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - The influence of guanyl-5′-yl imidodiphosphate and sodium on muscarinic receptor binding in the rat brain and longitudinal muscle of the rat ileum

AU - Ehlert, Frederick J.

AU - Roeske, William R.

AU - Rosenberger, Lois B.

AU - Yamamura, Henry I.

PY - 1980/1/21

Y1 - 1980/1/21

N2 - The effects of guanyl-5′-yl imidodiphosphate (Gpp(NH)p) and sodium on muscarinic receptor binding in the rat brain and longitudinal muscle of the rat ileum were investigated using the specific muscarinic affinity label [3H](-) quinuclidinyl benzilate ([3H](-)QNB). When measured by competitive inhibition of [3H](-)QNB binding to homogenates of the longitudinal muscle of the ileum, the IC50′s of oxotremorine and carbachol increased by a factor of 3 in the presence of 30 μM Gpp(NH)p. In contrast Gpp(NH)p only produced small increases in agonist IC50 values when binding experiments were done on various rat brain regions. The agonist inhibition curves deviated from the law of mass action and were consistant with a two binding site model. Nonlinear regression analysis showed variation in the percentage of high affinity agonist sites in the cerebellum (68%), brainstem (68%), longitudinal muscle of the ileum (44-50%) and forebrain (21-30%). In the ileum and forebrain, the predominant effect of Gpp(NH)p on agonist binding was a reduction in the affinity of the high affinity agonist binding site. In the cerebellum and brainstem Gpp(NH)p had no effect. Furthermore, Gpp(NH)p had no significant effect on antagonist binding in any tissue. The influence of sodium (200 mM NaCl) on muscarinic receptor binding was investigated in homogenates of the forebrain and longitudinal muscle of the ileum, and a preferential reduction of agonist affinity by sodium was observed.

AB - The effects of guanyl-5′-yl imidodiphosphate (Gpp(NH)p) and sodium on muscarinic receptor binding in the rat brain and longitudinal muscle of the rat ileum were investigated using the specific muscarinic affinity label [3H](-) quinuclidinyl benzilate ([3H](-)QNB). When measured by competitive inhibition of [3H](-)QNB binding to homogenates of the longitudinal muscle of the ileum, the IC50′s of oxotremorine and carbachol increased by a factor of 3 in the presence of 30 μM Gpp(NH)p. In contrast Gpp(NH)p only produced small increases in agonist IC50 values when binding experiments were done on various rat brain regions. The agonist inhibition curves deviated from the law of mass action and were consistant with a two binding site model. Nonlinear regression analysis showed variation in the percentage of high affinity agonist sites in the cerebellum (68%), brainstem (68%), longitudinal muscle of the ileum (44-50%) and forebrain (21-30%). In the ileum and forebrain, the predominant effect of Gpp(NH)p on agonist binding was a reduction in the affinity of the high affinity agonist binding site. In the cerebellum and brainstem Gpp(NH)p had no effect. Furthermore, Gpp(NH)p had no significant effect on antagonist binding in any tissue. The influence of sodium (200 mM NaCl) on muscarinic receptor binding was investigated in homogenates of the forebrain and longitudinal muscle of the ileum, and a preferential reduction of agonist affinity by sodium was observed.

UR - http://www.scopus.com/inward/record.url?scp=0018891963&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018891963&partnerID=8YFLogxK

U2 - 10.1016/0024-3205(80)90300-8

DO - 10.1016/0024-3205(80)90300-8

M3 - Article

C2 - 7360006

AN - SCOPUS:0018891963

VL - 26

SP - 245

EP - 252

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

IS - 3

ER -