Modulatory mechanisms in the isolated internally perfused ventricle of the whelk Busycon canaliculatum.
1. Isolated cannulated ventricles commenced spontaneous beating on application of perfusion pressure of 10 cm water. Complete hearts showed a fast patterned cyclical rhythm, whereas ventricles devoid of atrial material showed a continuous slow rhythm. 2. Perfused ventricles were inhibited by ACh with a threshold at 10(-8) mol l-1 and arrested at 10(-7) mol l-1, and ventricles under stimulation by 5HT could be arrested by ACh at this concentration. 3. Perfused ventricles were stimulated by 5HT, with threshold at 10(-9) mol l-1 and maximum at 10(-5) mol l-1. Metoclopramide was without affect on 5HT responses, but metitipine and methysergide did inhibit such responses suggesting that the 5HT receptor present possessed mixed properties of the vertebrate 5-HT1 and 5-HT2 receptor subtypes. 4. Ventricles were very sensitive to the excitatory actions of FMRFamide in the 10(-9) to 10(-5) mol l-1 range. Preparations were insensitive to GAPFLRFamide, but SCP-B was modestly excitatory (threshold 10(-7) mol l-1). 5. Preparations were not significantly affected by adenosine, ATP, and guanosine, but GTP was strongly excitatory at 10(-7) mol l-1. 6. 5HT and FMRFamide responses were additive. Preparations responded strongly to the adenylate cyclase activator forskolin and dibutyryl cAMP enhanced spontaneous contractions and 5HT responses, suggesting that the 5HT receptor may operate via a cAMP secondary mechanism. 7. The IP3 inhibitor lithium (10 mmol l-1), caused slight inhibition of FMRFamide responses, suggesting that the receptor to this peptide may operate via IP3 as a second messenger. 8. Neuromodulation in this preparation would appear to involve ACh as inhibitor, 5HT and FMRFamide as upregulators, with no clear roles for FMRFamide-related peptides and GTP.
Huddart
H
H
Division of Biological Sciences, Lancaster University, England.
Hill
R B
RB
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D019835:FMRFamide; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D008974:Mollusca / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D015290:Second Messenger Systems / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D016276:Ventricular Function
D009479:Neuropeptides; D018377:Neurotransmitter Agents; D011687:Purines; D012702:Serotonin Antagonists; D012701:Serotonin; D019835:FMRFamide; D006160:Guanosine Triphosphate; D008094:Lithium; D000109:Acetylcholine; D008784:Methysergide