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The sensitivity to sympathomimetic amines of isolated atria removed from sham-injected and 6-hydroxydopamine-treated (6-OHDA) guinea-pigs was examined in the presence of an extraneuronal uptake blocker and an alpha-adrenoceptor antagonist. Three weeks of pretreatment with 6-OHDA resulted in leftwards shifts of the dose-response curves for the positive chronotropic and inotropic responses of right and left atria to isoprenaline. The responses to the partial agonist salbutamol were also potentiated after 6-OHDA pretreatment, revealed as an increase in the maximum response relative to isoprenaline. The supersensitivity was post-synaptic in origin and independent of changes in disposition or metabolism, since it was observed with agonists immune to neuronal uptake and O-methylation, and in the presence of extraneuronal uptake inhibition by metanephrine. It was also specific for the beta-adrenoceptor, no supersensitivity to histamine being found. In the right atria, the supersensitivity was partially masked by an opposing depressant effect after 6-OHDA pretreatment which was observed with histamine. Dissociation constants (KA) for the left atrial inotropic responses to orciprenaline were determined by use of the antagonist Ro 03-7894. Atria from 6-OHDA-pretreated animals were supersensitive to orciprenaline, but the KA value did not differ from that after sham injection. It could therefore be concluded that the increase in sensitivity was not due to an increase in affinity for the beta-adrenoceptor.
R G Chess-Williams, and
P F Grassby, and
W Culling, and
W Penny, and
K J Broadley, and
D J Sheridan
January 1971,
Canadian journal of physiology and pharmacology,
R G Chess-Williams, and
P F Grassby, and
W Culling, and
W Penny, and
K J Broadley, and
D J Sheridan
May 1977,
Life sciences,
R G Chess-Williams, and
P F Grassby, and
W Culling, and
W Penny, and
K J Broadley, and
D J Sheridan
January 1987,
Journal of receptor research,
R G Chess-Williams, and
P F Grassby, and
W Culling, and
W Penny, and
K J Broadley, and
D J Sheridan
October 1973,
Nippon Ganka Gakkai zasshi,
R G Chess-Williams, and
P F Grassby, and
W Culling, and
W Penny, and
K J Broadley, and
D J Sheridan
October 1970,
Nature,
R G Chess-Williams, and
P F Grassby, and
W Culling, and
W Penny, and
K J Broadley, and
D J Sheridan
January 1982,
The Journal of pharmacology and experimental therapeutics,
R G Chess-Williams, and
P F Grassby, and
W Culling, and
W Penny, and
K J Broadley, and
D J Sheridan
June 1974,
Canadian journal of physiology and pharmacology,
R G Chess-Williams, and
P F Grassby, and
W Culling, and
W Penny, and
K J Broadley, and
D J Sheridan
November 1969,
The Journal of pharmacology and experimental therapeutics,
R G Chess-Williams, and
P F Grassby, and
W Culling, and
W Penny, and
K J Broadley, and
D J Sheridan
September 1973,
British journal of pharmacology,
R G Chess-Williams, and
P F Grassby, and
W Culling, and
W Penny, and
K J Broadley, and
D J Sheridan
January 1973,
Surgical forum,
