Opioid receptors and prejunctional modulation of capsaicin-sensitive sensory nerves in guinea-pig left atrium.
1. In the isolated electrically driven left atria from reserpine-pretreated guinea-pigs and in presence of 1 microM atropine, electrical field stimulation (EFS) at 10 Hz produces a delayed positive inotropic response (DPIR) involving activation of capsaicin-sensitive afferents. 2. Opioids inhibited the DPIR with the following order of potency: dermorphin greater than [D-Ala2,N-MePhe4, Gly5-ol]-enkephalin (DAGO) greater than or equal to [D-Ala2,D-Leu5]-enkephalin (DADLE) greater than morphine greater than dynorphin A (1-13) greater than [D-Pen2,D-Pen5]-enkephalin (DPDPE). U-50488 was ineffective up to 10 microM. 3. Opioids also inhibited resting inotropism (3 Hz) with the following rank order of potency: DADLE greater than DAGO greater than U-50488 = dynorphin A (1-13) = morphine = DPDPE. 4. Both inhibition of the DPIR and inhibition of resting inotropism were prevented by 10 microM naloxone. 5. Neither dermorphin (0.1 microM) nor DAGO (0.3 microM) or DADLE (1 microM) inhibit responses produced by capsaicin (30 nM) or calcitonin gene-related peptide (3 nM). 6. These findings indicate that capsaicin-sensitive nerves in the guinea-pig atrium are endowed with mu opioid receptors which inhibit transmitter release when sensory nerve terminals are activated by EFS but not by capsaicin.
Giuliani
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S
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Maggi
C A
CA
Meli
A
A
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D004399:Dynorphins / Q000494:pharmacology; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D004745:Enkephalins / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology; D018847:Opioid Peptides; D010446:Peptide Fragments / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D017450:Receptors, Opioid, mu; D012110:Reserpine / Q000494:pharmacology
D004745:Enkephalins; D009842:Oligopeptides; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C030058:dermorphin; D009270:Naloxone; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; C026843:dynorphin (1-13); D004399:Dynorphins; D001285:Atropine; D020881:Enkephalin, D-Penicillamine (2,5)-; D012110:Reserpine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin