Role of G-proteins and adenylate cyclase in antinociception produced by intrathecal purines

Jana Sawynok; Allison Reid

doi:10.1016/0014-2999(88)90143-4

Role of G-proteins and adenylate cyclase in antinociception produced by intrathecal purines

Jana Sawynok, Allison Reid

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

Abstract

The effects of pertussis toxin, forskolin and phosphodiesterase inhibitors on the antinociceptive action of intrathecal purines were examined to investigate the possible involvement of adenylate cyclase in spinal antinociception. Pretreatment with pertussis toxin (0.25 and 0.5 μg) inhibited the antinociceptive action of L-phenyl-isopropyladenosine (L-PIA), N⁶-cyclohexyladenosine (CHA) and 5′-N-ethylcarboxamide adenosine (NECA) in the tail flick and hot plate tests. Forskolin (10-30 μg) reduced the effect of CHA and NECA in the hot plate test. Ro 201724 (30 μg) and Rolipram (20 μg) inhibited CHA in the tail flick and hot plate tests, but did not affect NECA in either test. These results suggest (1) spinal antinociception by purines is mediated by interactions with G-proteins (G_i linked to adenylate cyclase and/or G_o linked to ion channels) (2) spinal antinociception by CHA is due to inhibition of adenylate cyclase (3) a separate mechanism, which does not involve stimulation of adenylate cyclase, may be involved in the spinal action of NECA.

Original language	English
Pages (from-to)	25-34
Number of pages	10
Journal	European Journal of Pharmacology
Volume	156
Issue number	1
DOIs	https://doi.org/10.1016/0014-2999(88)90143-4
Publication status	Published - Oct 26 1988

Bibliographical note

Funding Information:
This work was supported by the Medical Research Council of Canada in a grant to J.S. We thank Hoffman-La Roche Ltd., Ontario and Schering, Berlin for the supply of Ro 201724 and Rolipram respectively.

ASJC Scopus Subject Areas

Pharmacology

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10.1016/0014-2999(88)90143-4

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title = "Role of G-proteins and adenylate cyclase in antinociception produced by intrathecal purines",

abstract = "The effects of pertussis toxin, forskolin and phosphodiesterase inhibitors on the antinociceptive action of intrathecal purines were examined to investigate the possible involvement of adenylate cyclase in spinal antinociception. Pretreatment with pertussis toxin (0.25 and 0.5 μg) inhibited the antinociceptive action of L-phenyl-isopropyladenosine (L-PIA), N6-cyclohexyladenosine (CHA) and 5′-N-ethylcarboxamide adenosine (NECA) in the tail flick and hot plate tests. Forskolin (10-30 μg) reduced the effect of CHA and NECA in the hot plate test. Ro 201724 (30 μg) and Rolipram (20 μg) inhibited CHA in the tail flick and hot plate tests, but did not affect NECA in either test. These results suggest (1) spinal antinociception by purines is mediated by interactions with G-proteins (Gi linked to adenylate cyclase and/or Go linked to ion channels) (2) spinal antinociception by CHA is due to inhibition of adenylate cyclase (3) a separate mechanism, which does not involve stimulation of adenylate cyclase, may be involved in the spinal action of NECA.",

author = "Jana Sawynok and Allison Reid",

note = "Funding Information: This work was supported by the Medical Research Council of Canada in a grant to J.S. We thank Hoffman-La Roche Ltd., Ontario and Schering, Berlin for the supply of Ro 201724 and Rolipram respectively.",

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N2 - The effects of pertussis toxin, forskolin and phosphodiesterase inhibitors on the antinociceptive action of intrathecal purines were examined to investigate the possible involvement of adenylate cyclase in spinal antinociception. Pretreatment with pertussis toxin (0.25 and 0.5 μg) inhibited the antinociceptive action of L-phenyl-isopropyladenosine (L-PIA), N6-cyclohexyladenosine (CHA) and 5′-N-ethylcarboxamide adenosine (NECA) in the tail flick and hot plate tests. Forskolin (10-30 μg) reduced the effect of CHA and NECA in the hot plate test. Ro 201724 (30 μg) and Rolipram (20 μg) inhibited CHA in the tail flick and hot plate tests, but did not affect NECA in either test. These results suggest (1) spinal antinociception by purines is mediated by interactions with G-proteins (Gi linked to adenylate cyclase and/or Go linked to ion channels) (2) spinal antinociception by CHA is due to inhibition of adenylate cyclase (3) a separate mechanism, which does not involve stimulation of adenylate cyclase, may be involved in the spinal action of NECA.

AB - The effects of pertussis toxin, forskolin and phosphodiesterase inhibitors on the antinociceptive action of intrathecal purines were examined to investigate the possible involvement of adenylate cyclase in spinal antinociception. Pretreatment with pertussis toxin (0.25 and 0.5 μg) inhibited the antinociceptive action of L-phenyl-isopropyladenosine (L-PIA), N6-cyclohexyladenosine (CHA) and 5′-N-ethylcarboxamide adenosine (NECA) in the tail flick and hot plate tests. Forskolin (10-30 μg) reduced the effect of CHA and NECA in the hot plate test. Ro 201724 (30 μg) and Rolipram (20 μg) inhibited CHA in the tail flick and hot plate tests, but did not affect NECA in either test. These results suggest (1) spinal antinociception by purines is mediated by interactions with G-proteins (Gi linked to adenylate cyclase and/or Go linked to ion channels) (2) spinal antinociception by CHA is due to inhibition of adenylate cyclase (3) a separate mechanism, which does not involve stimulation of adenylate cyclase, may be involved in the spinal action of NECA.

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Role of G-proteins and adenylate cyclase in antinociception produced by intrathecal purines

Abstract

Bibliographical note

ASJC Scopus Subject Areas

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