Title: The P2Y1 receptor in the colonic myenteric plexus of rats and its correlation with opioid-
induced constipation
Version: 3 Date: 12 Nov 2023
Reviewer's report:
1. General comment
This paper by Zhao et al. entitled "The P2Y1 receptor in the colonic myentric layer of rats
and its correlation with opioid-induced constipation" is an interesting study on opioid-induced
constipation was associated with alteration in the function and expression levels of P2Y1
receptors in rat colonic myenteric layers.
In general, this is a well-written paper. These findings will be interesting for gastrointestinal and
general practitioners as well as researchers in those field. But before this paper will be reached
to the criteria, the authors should be answered the mentioned below.
2. Major comments
(1) Opioid-induced constipation means narcotic analgesic user suffer from constipation. The
Loperamide treatment is the antidiarrheal agents, but not narcotic analgesia.  Therefore,
the author described that Loperamide-induced constipation mean as the opioid-induced
constipation. It is difficult to understand your concept.
(2) Figure 2, 3, and Table1, did you study the effect of naloxone, opioid a #-receptor antagonist,
on loperamide-induced constipation in rat.
(3) The author should mention about the role of serotonin in opioid-induced constipation as well
as P2Y receptors in discussion.
3. Minor comments
(1) Page numbers should be put on your paper.  It was difficult for us to read and find out
keywords.
(2) The author should describe more about the selectivity or affinity of MRS2500, a P2Y1
receptor antagonist, as compared with MRS 2179 in “materials and methods”.
(3) Page 7 Line 7 from the bottom, “ZYQ” should be removed on your paper.
(4) Pape 10 Figure3, MOR in rat colonic colonic muscle layer.  Should be removed the second
“colonic”.
(5) Page 12 Line 12, OIC is is characterized by ~. Should be removed the second “is”.
Title: The P2Y1 receptor in the colonic myenteric plexus of rats and its correlation with opioid-
induced constipation
Version: 3 Date: 12 Nov 2023
Reviewer's report:
1. General comment
This paper by Zhao et al. entitled "The P2Y1 receptor in the colonic myentric layer of rats
and its correlation with opioid-induced constipation" is an interesting study on opioid-induced
constipation was associated with alteration in the function and expression levels of P2Y1
receptors in rat colonic myenteric layers.
In general, this is a well-written paper. These findings will be interesting for gastrointestinal and
general practitioners as well as researchers in those field. But before this paper will be reached
to the criteria, the authors should be answered the mentioned below.
2. Major comments
(1) Opioid-induced constipation means narcotic analgesic user suffer from constipation. The
Loperamide treatment is the antidiarrheal agents, but not narcotic analgesia.  Therefore,
the author described that Loperamide-induced constipation mean as the opioid-induced
constipation. It is difficult to understand your concept.
(2) Figure 2, 3, and Table1, did you study the effect of naloxone, opioid a #-receptor antagonist,
on loperamide-induced constipation in rat.
(3) The author should mention about the role of serotonin in opioid-induced constipation as well
as P2Y receptors in discussion.
3. Minor comments
(1) Page numbers should be put on your paper.  It was difficult for us to read and find out
keywords.
(2) The author should describe more about the selectivity or affinity of MRS2500, a P2Y1
receptor antagonist, as compared with MRS 2179 in “materials and methods”.
(3) Page 7 Line 7 from the bottom, “ZYQ” should be removed on your paper.
(4) Pape 10 Figure3, MOR in rat colonic colonic muscle layer.  Should be removed the second
“colonic”.
(5) Page 12 Line 12, OIC is is characterized by ~. Should be removed the second “is”.
Please review this paper.
user
Title: The P2Y1 receptor in the colonic myenteric plexus of rats and its correlation with opioid-
induced constipation
Version: 3 Date: 12 Nov 2023
Reviewer's report:
1. General comment
This paper by Zhao et al. entitled "The P2Y1 receptor in the colonic myentric layer of rats
and its correlation with opioid-induced constipation" is an interesting study on opioid-induced
constipation was associated with alteration in the function and expression levels of P2Y1
receptors in rat colonic myenteric layers.
In general, this is a well-written paper. These findings will be interesting for gastrointestinal and
general practitioners as well as researchers in those field. But before this paper will be reached
to the criteria, the authors should be answered the mentioned below.
2. Major comments
(1) Opioid-induced constipation means narcotic analgesic user suffer from constipation. The
Loperamide treatment is the antidiarrheal agents, but not narcotic analgesia.  Therefore,
the author described that Loperamide-induced constipation mean as the opioid-induced
constipation. It is difficult to understand your concept.
(2) Figure 2, 3, and Table1, did you study the effect of naloxone, opioid a #-receptor antagonist,
on loperamide-induced constipation in rat.
(3) The author should mention about the role of serotonin in opioid-induced constipation as well
as P2Y receptors in discussion.
3. Minor comments
(1) Page numbers should be put on your paper.  It was difficult for us to read and find out
keywords.
(2) The author should describe more about the selectivity or affinity of MRS2500, a P2Y1
receptor antagonist, as compared with MRS 2179 in “materials and methods”.
(3) Page 7 Line 7 from the bottom, “ZYQ” should be removed on your paper.
(4) Pape 10 Figure3, MOR in rat colonic colonic muscle layer.  Should be removed the second
“colonic”.
(5) Page 12 Line 12, OIC is is characterized by ~. Should be removed the second “is”.
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