Biomedical subjects

J R Mathiasen

Publications and source records attributed to J R Mathiasen.

25 records · Page 2Linked to original sources

PubMed1987

Colonic bead expulsion time in normal and mu-opioid receptor deficient (CXBK) mice following central (ICV) administration of mu- and delta-opioid agonists.

A method utilizing the insertion of a 3 mm glass bead into the distal colon was used to evaluate the activity of intracerebroventricularly (ICV) administered mu- and delta-opioid agonists on colonic bead expulsion time in mice. Specifically, the ability of two mu-opioid receptor agonists, morphine and [D-Ala2,NMePhe4, Gly-ol5]-enkephalin (DAGO) and a selective delta-opioid receptor agonist, [D-Pen2,L-Pen5]-enkephalin (DPLPE), to inhibit colonic bead expulsion time was measured in normal (Swiss) and mu-opioid deficient (CXBK) mice. All three compounds maximally inhibited colonic bead expulsion time in normal mice. All three compounds also inhibited colonic bead expulsion time in CXBK mice, but none maximally. These results are in contrast to previous work in which clear differential analgesic sensitivity of CXBK mice to centrally administered mu- and delta-opioid receptor agonists was observed in the tail-flick test. Taken together, the results suggest (a) that mu-, and possibly delta-, opioid receptors can mediate supraspinal inhibition of colonic bead expulsion in mice and (b) that the genetic deficits of mu-receptor number or genetically-induced alteration in receptor function in CXBK mice do not equally affect inhibition of colonic bead expulsion and tail-flick antinociception.

Animals↗

PubMed1987

Evidence that reciprocal hindlimb scratching elicited in mice by intrathecal administration of muscarinic agonists is mediated through M1 type receptors.

Intrathecal (IT) administration of pilocarpine to mice produces a vigorous and dose-related reciprocal hindlimb scratching (RHS) response (ED50 = 0.6 microgram) that is potently blocked by simultaneous IT administration of atropine (ID50 = 0.002 microgram). We now report that RHS is (1) also elicited by the more selective M1 agonist McN-A-343-11 (ED50 = 11.6 micrograms), (2) blocked by the selective M1 antagonist pirenzepine (ID50 = 0.001 microgram), and (3) is not blocked by the selective M2 antagonist AF-DX 116 BS at a dose up to 100 times the ID50 dose of pirenzepine. These results extend our earlier findings and suggest that the RHS elicited in mice by IT injection of muscarinic agonists is mediated through pirenzepine-sensitive (presumably M1) receptors and that RHS may be a convenient in vivo centrally mediated M1 endpoint.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

PubMed1987

Restoration of analgesic response of C57BL/6J-bgJ (beige-J) mice to morphine by carbachol.

C57BL/6J-bgJ (beige-J) mice respond poorly to the analgesic effects of centrally administered (intracerebroventricular; i.c.v.) morphine in the tail-flick test. In the present study C57BL/6J-bgJ mice, their littermate (heterozygous) controls, and normal Swiss mice were given carbachol (200 micrograms/ml) in their drinking water for three weeks. Carbachol had no effect on control animals. However, the carbachol-treated beige-J mice responded to i.c.v.-administered morphine (1 microgram) significantly better than untreated beige-J mice and nearly as well as the normal mice.

Animals↗

PubMed1987

C57BL/6J-bgJ (beige) mice: differential sensitivity in the tail flick test to centrally administered mu- and delta-opioid receptor agonists.

The antinociceptive effects of two mu-opioid receptor agonists, morphine and [D-Ala2, MePhe4, Gly-ol5]enkephalin (DAGO), and a selective delta-receptor agonist, [D-Pen2, L-Pen5]enkephalin (DPLPE), were determined in C57BL/6J-bgJ (beige) and control mice (CRS-CDl and C57BL/6By) using a standard tail-flick assay. The antinociceptive response of C57BL/6J-bgJ mice to intracerebro-ventricularly administered morphine and DAGO was significantly reduced compared to controls, but there was no difference in the antinociceptive response to DPLPE. These results suggest that there is a genetic deficit of mu-opioid receptor number or a genetically-induced alteration in receptor function in regions of C57BL/6J-bgJ brains involved in antinociception, that delta-opioid receptors can mediate antinociception in mice, and that the C57BL/6J-bgJ strain may offer a practical new animal model for studying the function of opioid receptor subtypes.

Animals↗

PubMed1987

[D-Pen2,L-Pen5]enkephalin induced analgesia in the jimpy mouse: in vivo evidence for delta-receptor mediated analgesia.

Jimpy (B6CBA-A W-J/A-Ta jp) mice, which are known to be deficient in neuronal cerebroside sulfate (a putative component of the mu opioid receptor), were non-responsive in the tail flick test (compared to littermate controls and a standard Swiss strain of mouse) to analgesic doses of two mu opioid receptor agonists, morphine sulfate and [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO). However, the jimpy mice responded normally (compared to controls) to the analgesic effects of the selective delta opioid receptor agonist [D-Pen2,L-Pen5]enkephalin (DPLPE). These results suggest (1) that delta opioid receptors can mediate analgesia and (2) that cerebroside sulfate is not necessary for delta opioid receptor activation.

Analgesics↗

PubMed1986

Effects of mefenidil hydrochloride on cerebral blood flow in conscious and anesthetized rat.

The purpose of this study was to determine the effects of the putative cerebral vasodilator, mefenidil hydrochloride (MF), on cardiocirculatory dynamics and the total distribution of cardiac output in the conscious rat. The radioactive microsphere technique was used to measure regional blood flow and cardiac output before (control) and during intravenous infusion of either MF (2.5, 5.0, 10.0 mg/kg) or vehicle (VH; saline, 0.0204, 0.0408. 0.0816 ml/min, respectively). Neither MF nor VH were found to have significant effects on cerebral blood flow or vascular resistance in conscious rats. MF significantly increased cerebral blood flow and lowered cerebral vascular resistance compared to VH in anesthetized animals without having significant effects in other circulatory regions.

Animals↗

PubMedDate not supplied

[3H][D-Ala2,NMePhe4,Gly-ol5]-enkephalin (mu-opioid) binding in beige-J mice.

Tritiated [D-Ala2,NMePhe4,Gly-ol5]-enkephalin ([3H]DAGO) was used to examine mu-opioid receptor number and mu-ligand binding in brain synaptic membranes (P2 fraction) from C57BL/6J-bgJ/bgJ (beige-J) mice, a strain with combined deficiencies in immunological function (resembling Chediak-Higashi syndrome) and analgesic response to mu-opioid agonists such as morphine and DAGO. As controls, white mice, beige-J littermates (normally responsive to mu-opioid agonists), and a known mu-deficient strain (CXBK) were also examined. Neither the KD (0.47 to 0.49 nM) nor the Bmax (153 to 168 fmol/mg protein) determined for beige-J mice was significantly different from values determined for littermates or white mice. In contrast, the Bmax of CXBK mice (66 fmol/mg protein) was clearly less than that of the other strains. The analgesic defect of beige-J mice, therefore, is not likely due to an insufficient number of mu-opioid receptors, as it presumably is in CXBK mice. Carbachol (200 micrograms/ml), which partly corrects the analgesic defect of beige-J mice, had no effect on [3H]DAGO binding either acutely in vitro or chronically ex vivo after administration to beige-J mice for three weeks. Hence, the analgesic defect of beige-J mice appears to be due to some defect in the mu-opioid receptor-effector coupling mechanism or to some endogenous substance that inhibits binding of mu-opioid ligands to otherwise functional receptors.

Animals↗