Histamine Receptor Assays

Nigel P. Shankley1, Magda F. Morton1, Gillian F. Watt2

1 R.W. Johnson Pharmaceutical Research Institute, La Jolla, California, 2 James Black Foundation Ltd., London, United Kingdom
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 4.17
DOI:  10.1002/0471141755.ph0417s14
Online Posting Date:  November, 2001
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Abstract

This unit describes three standard in vitro bioassays for studying histamine H1, H2 and H3 receptors in isolated intact tissues removed from the guinea pig. Both the H1 and H3 receptor assays are based on preparations of the ileum, whereas the spontaneously beating right atrium assay is used for the H2ÔÇÉreceptor.

This unit describes three standard in vitro bioassays for studying histamine H1, H2 and H3 receptors in isolated intact tissue.

     
 
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Table of Contents

  • Basic Protocol 1: Histamine H1 Receptors: Guinea Pig Ileum
  • Basic Protocol 2: Histamine H2 Receptors: Guinea Pig Right Atrium
  • Basic Protocol 3: Histamine H3 Receptors: Electrically Stimulated Guinea Pig Ileum
  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

Basic Protocol 1: Histamine H1 Receptors: Guinea Pig Ileum

  Materials
  • Male Hartley guinea pig, 200 to 450 g (Charles River Labs)
  • CO 2 gas cylinder or dry ice pellets
  • Modified Krebs‐Henseleit solution (see recipe in unit 4.15) freshly prepared and continuously gassed with 95% O 2/5% CO 2through a fine glass sinter (begin gassing after mixing stock solutions A and B but before adding stock solution C)
  • 95% O 2/5% CO 2 (v/v) cylinders with regulators capable of delivering 5 to 15 psi
  • 100 mM histamine stock solution (see recipe for standard histamine agonist stock solutions)
  • 100 mM methacholine stock solution (see recipe)
  • Standard histamine H 1 receptor antagonist stock solutions (see recipe): e.g., mepyramine (also known as pyrilamene; Sigma), triprolidine (Sigma)
  • Test compound(s)
  • Airtight euthanasia chamber large enough to accommodate guinea pig
  • Guillotine
  • Fine forceps and scissors
  • Glass Pasteur pipets: 13.8 cm length, 0.65 cm external diameter
  • Cotton wool
  • Surgical silk (1.0)
  • Isotonic transducer (Hugo Sachs Elektronik, type 373)
  • Standard tissue bath equipment (unit 4.4), including:
  •  Fixed tissue holder
  •  Thermostatically regulated water circulator
  •  Polygraph/chart recorder/PC‐based data acquisition system
  • Additional reagents and equipment for dissecting the ileum longitudinal muscle (unit 4.13)

Basic Protocol 2: Histamine H2 Receptors: Guinea Pig Right Atrium

  Materials
  • Male Hartley guinea pig, 200 to 450 g (Charles River Labs)
  • CO 2 gas cylinder or dry ice pellets
  • Modified Krebs‐Henseleit solution (see recipe in unit 4.15) freshly prepared and continuously gassed with 95% O 2/5% CO 2through a fine glass sinter (begin gassing after mixing stock solutions A and B but before adding stock solution C)
  • 95% (v/v) O 2/5% CO 2 cylinders with regulators capable of delivering 5 to 15 psi
  • 100 mM histamine stock solution (see recipe for standard histamine agonist stock solutions)
  • 100 mM propranolol or timolol stock solutions (see recipe)
  • Standard histamine H 2 receptor antagonists (see recipe for standard histimine antagonist stock solutions): e.g., cimetidine, famotidine (Sigma)
  • Test compound(s)
  • Airtight euthanasia chamber large enough to accommodate guinea pig
  • Guillotine
  • Fine forceps and scissors
  • Surgical silk (1.0)
  • Isometric transducer (Grass Instruments FT.03)
  • Standard tissue bath equipment (unit 4.4) including:
    •  Fixed tissue holder and stainless steel tissue suspension wire
    •  Thermostatically regulated water circulator
    •  Polygraph/chart recorder/PC‐based data acquisition system
    •  Ratemeter (see unit 4.6 for details)
  • Additional reagents and equipment for dissecting the right atrium (unit 4.3)

Basic Protocol 3: Histamine H3 Receptors: Electrically Stimulated Guinea Pig Ileum

  Materials
  • Male Hartley guinea pig, 200 to 450 g (Charles River Labs)
  • CO 2 gas cylinder or dry ice pellets
  • Modified Krebs‐Henseleit solution (see recipe in unit 4.15) containing 3 µM mepyramine (H 1 receptor antagonist; Sigma) and 10 µM famotidine (H 2 receptor antagonist; Sigma) freshly prepared and continuously gassed with 95% O 2/5% CO 2through a fine glass sinter (begin gassing after mixing stock solutions A and B but before adding stock solution C)
  • 95% (v/v) O 2/5% CO 2 cylinders with regulators capable of delivering 5 to 15 psi
  • R‐α‐methylhistamine stock solution (see recipe for standard histamine agonist stock solutions Sigma;)
  • Standard histamine H 3‐receptor agonists (see recipe): e.g., R‐α‐methylhistamine (Sigma), imetit, immepip (Tocris)
  • Standard histamine H 3‐receptor antagonists (see recipe): e.g., thioperamide (Sigma), clobenpropit (RBI)
  • Test compound(s)
  • Airtight euthanasia chamber large enough to accommodate guinea pig
  • Guillotine
  • Fine forceps and scissors
  • Glass Pasteur pipets: 13.8 cm length, 0.65 cm external diameter
  • Surgical silk (1.0)
  • Isometric transducer (Grass FT03)
  • Standard tissue bath equipment (also see unit 4.4) including:
    •  Fixed tissue holder
    •  Platinum electrodes (length 0.76 cm, diameter 0.06 cm)
    •  Electrical stimulator (e.g., Grass Instruments S88 plus Grass stimulator isolation units or Digitimer Multistim D330)
    •  Polygraph/chart recorder/PC‐based data acquisition system
    •  Thermostatically regulated water circulator
  • Additional reagents and equipment for dissecting the ileum longitudinal muscle (unit 4.13)
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Figures

Videos

Literature Cited

Literature Cited
   Angus, J.A. and Black, J.W. 1980. Pharmacological analysis of cardiac H2 receptor blockade by amitriptyline and lysergic acid diethylamide. Circ. Res. 65:1‐109.
   Arrang, J.M., Garbarg, M., and Schwartz, J.C. 1983. Auto‐inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature 302:1‐5.
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   Ash, A.S.F. and Schild, H.O. 1966. Receptors mediating some actions of histamine. Br. J. Pharmacol. 27:427‐439.
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   Taylor, S.J. and Kilpatrick, G.J. 1992. Characterisation of histamine H3 receptors controlling non‐adrenergic non‐cholinergic contractions of the guinea‐pig isolated ileum. Br. J. Pharmacol. 105:667‐674.
   Trzeciakowski, J.P. 1987. Inhibition of guinea‐pig ileum contractions mediated by a class of histamine receptor resembling the H3 subtype. J. Pharmacol. Exp. Ther. 243:874‐880.
   Watt, G.F., Hamilton, L.C., Shankley, N.P., and Black, J.W. 1997. Analysis of H1‐, H2‐ and H3‐receptor‐mediated components of the response to histamine in guinea‐pig isolated ileum. Br. J. Pharmacol. 122:434.
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